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Identification
Name Verapamil
Accession Number DB00661 (APRD00335)
Type small molecule
Groups approved
Description

A calcium channel blocker that is a class IV anti-arrhythmia agent. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Verapamil [Usan:Ban:Inn]
Verapamil HCl
Verapamilo [INN-Spanish]
Verapamilum [INN-Latin]
Salts Not Available
Brand names
Name Company
Apo-Verap
Arpamyl
Berkatens
Calan
Calan SR
Cardiagutt
Cardibeltin
Cordilox
Covera-HS
Dignover
Dilacoran
Drosteakard
Geangin
Iproveratril
Isoptimo
Isoptin
Isoptin SR
Novo-Veramil
NU-Verap
Quasar
Securon
Univer
Vasolan
Veracim
Veramex
Veraptin
Verelan
Verelan PM
Verexamil
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Brand mixtures
Brand Name Ingredients
Tarka trandolapril + verapamil hydrochloride
Categories
  • Vasodilator Agents
  • Antiarrhythmic Agents
  • Calcium Channel Blockers
  • Anti-Arrhythmia Agents
CAS number 52-53-9
Weight Average: 454.6016
Monoisotopic: 454.283157714
Chemical Formula C27H38N2O4
InChI Key InChIKey=SGTNSNPWRIOYBX-UHFFFAOYSA-N
InChI
InChI=1S/C27H38N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,8,13-16H2,1-7H3
Plain Text
IUPAC Name
2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
SMILES
COC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Catecholamines and Derivatives
Substructures
  • Phenols and Derivatives
  • Nitriles and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Cumenes and Derivatives
  • Cyanides
  • Aliphatic and Aryl Amines
  • Catechols
  • Phenethylamines
  • Aromatic compounds
  • Anisoles
  • Phenyl Esters
  • Catecholamines and Derivatives
Pharmacology
Indication For the treatment of hypertension, angina, and cluster headache prophylaxis.
Pharmacodynamics Verapamil is an L-type calcium channel blocker that also has antiarrythmic activity. The R-enantiomer is more effective at reducing blood pressure compared to the S-enantiomer. However, the S-enantiomer is 20 times more potent than the R-enantiomer at prolonging the PR interval in treating arrhythmias.
Mechanism of action Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known.
Absorption 90%
Volume of distribution Not Available
Protein binding 90%
Metabolism Not Available
Route of elimination Approximately 70% of an administered dose is excreted as metabolites in the urine and 16% or more in the feces within 5 days. About 3% to 4% is excreted in the urine as unchanged drug.
Half life 2.8-7.4 hours
Clearance Not Available
Toxicity LD50=8 mg/kg (i.v. in mice)
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00375 Verapamil Pathway SMP00375
Pharmacoeconomics
Manufacturers
  • Mylan pharmaceuticals inc
  • Elan drug delivery inc
  • Gd searle llc
  • Fsc laboratories inc
  • Abraxis pharmaceutical products
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • International medication system
  • Luitpold pharmaceuticals inc
  • Marsam pharmaceuticals llc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Ranbaxy laboratories inc
  • Glenmark generics ltd
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Par pharmaceutical inc
  • Pliva inc
  • Actavis elizabeth llc
  • Heritage pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Sandoz inc
  • Warner chilcott div warner lambert co
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Capsule, extended release Oral
Liquid Intravenous
Solution Intravenous
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Verelan 360 mg 24 Hour Capsule 6.82 USD capsule
Verelan 360 mg cap pellet 6.73 USD pellet
Verelan pm 300 mg cap pellet 5.87 USD pellet
Verelan 240 mg 24 Hour Capsule 4.76 USD capsule
Verelan 240 mg cap pellet 4.58 USD pellet
Verelan 180 mg 24 Hour Capsule 4.22 USD capsule
Verelan 180 mg cap pellet 4.06 USD pellet
Verelan pm 200 mg cap pellet 4.04 USD pellet
Verelan 120 mg cap pellet 3.87 USD pellet
Verapamil HCl CR 300 mg 24 Hour Capsule 3.82 USD capsule
Isoptin sr 240 mg tablet 3.32 USD tablet
Verapamil hcl powder 3.24 USD g
Calan SR 240 mg Controlled Release Tabs 3.15 USD tab
Isoptin SR 240 mg Controlled Release Tabs 3.14 USD tab
Verelan pm 100 mg cap pellet 3.13 USD pellet
Calan sr 240 mg caplet 3.09 USD caplet
Covera-HS 240 mg 24 Hour tablet 3.09 USD tablet
Covera-hs 240 mg tablet sa 2.97 USD tablet
Isoptin sr 180 mg tablet 2.9 USD tablet
Calan SR 180 mg Controlled Release Tabs 2.8 USD tab
Isoptin SR 180 mg Controlled Release Tabs 2.74 USD tab
Calan sr 180 mg caplet 2.7 USD caplet
Verapamil HCl CR 200 mg 24 Hour Capsule 2.62 USD capsule
Isoptin sr 120 mg tablet 2.29 USD tablet
Calan SR 120 mg Controlled Release Tabs 2.27 USD tab
Covera-HS 180 mg 24 Hour tablet 2.2 USD tablet
Isoptin SR 120 mg Controlled Release Tabs 2.16 USD tab
Calan sr 120 mg caplet 2.13 USD caplet
Covera-hs 180 mg tablet sa 2.11 USD tablet
Verapamil HCl CR 360 mg 24 Hour Capsule 2.1 USD capsule
Verapamil HCl CR 100 mg 24 Hour Capsule 2.04 USD capsule
Isoptin Sr 240 mg Sustained-Release Tablet 2.03 USD tablet
Calan sr 240 mg caplet sa 1.77 USD caplet
Verapamil HCl CR 240 mg 24 Hour Capsule 1.69 USD capsule
Verapamil HCl CR 240 mg Controlled Release Tabs 1.6 USD tab
Calan 120 mg tablet 1.56 USD tablet
Isoptin Sr 180 mg Sustained-Release Tablet 1.52 USD tablet
Verapamil HCl CR 180 mg 24 Hour Capsule 1.5 USD capsule
Calan sr 180 mg caplet sa 1.46 USD caplet
Verapamil HCl CR 120 mg 24 Hour Capsule 1.43 USD capsule
Verapamil HCl CR 180 mg Controlled Release Tabs 1.41 USD tab
Isoptin Sr 120 mg Sustained-Release Tablet 1.34 USD tablet
Calan 80 mg tablet 1.25 USD tablet
Verapamil 2.5 mg/ml vial 1.18 USD ml
Verapamil HCl CR 120 mg Controlled Release Tabs 1.12 USD tab
Apo-Verap Sr 240 mg Sustained-Release Tablet 0.91 USD tablet
Mylan-Verapamil Sr 240 mg Sustained-Release Tablet 0.91 USD tablet
Novo-Veramil Sr 240 mg Sustained-Release Tablet 0.91 USD tablet
Pms-Verapamil Sr 240 mg Sustained-Release Tablet 0.91 USD tablet
Calan 40 mg tablet 0.76 USD tablet
Apo-Verap Sr 120 mg Sustained-Release Tablet 0.72 USD tablet
Mylan-Verapamil Sr 120 mg Sustained-Release Tablet 0.72 USD tablet
Verapamil HCl 120 mg tablet 0.71 USD tablet
Apo-Verap Sr 180 mg Sustained-Release Tablet 0.69 USD tablet
Mylan-Verapamil Sr 180 mg Sustained-Release Tablet 0.69 USD tablet
Verapamil HCl 80 mg tablet 0.56 USD tablet
Apo-Verap 120 mg Tablet 0.45 USD tablet
Mylan-Verapamil 120 mg Tablet 0.45 USD tablet
Nu-Verap 120 mg Tablet 0.45 USD tablet
Verapamil 120 mg tablet 0.39 USD tablet
Verapamil 80 mg tablet 0.31 USD tablet
Verapamil HCl 40 mg tablet 0.29 USD tablet
Apo-Verap 80 mg Tablet 0.29 USD tablet
Mylan-Verapamil 80 mg Tablet 0.29 USD tablet
Nu-Verap 80 mg Tablet 0.29 USD tablet
Verapamil 40 mg tablet 0.28 USD tablet
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6096339 1997-04-04 2017-04-04
United States 5785994 1992-10-22 2009-10-22
Properties
State liquid
Experimental Properties
Property Value Source
melting point < 25 °C PhysProp
boiling point 243-246 °C at 1.00E-02 mm Hg PhysProp
water solubility 4.47 mg/L Not Available
logP 3.79 HANSCH,C ET AL. (1995)
Caco2 permeability -4.58 ADME Research, USCD
pKa 8.92 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 3.94e-03 g/l ALOGPS
logP 5.23 ALOGPS
logP 5.04 ChemAxon
logS -5.1 ALOGPS
pKa (strongest basic) 9.68 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 63.95 ChemAxon
rotatable bond count 13 ChemAxon
refractivity 132.65 ChemAxon
polarizability 51.7 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Bellamy WT: P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol. 1996;36:161-83. Pubmed
External Links
Resource Link
KEGG Drug D02356 Link_out
KEGG Compound C07188 Link_out
PubChem Compound 2520 Link_out
PubChem Substance 46508158 Link_out
ChemSpider 2425 Link_out
BindingDB 50005628 Link_out
ChEBI 9948 Link_out
ChEMBL 9948 Link_out
Therapeutic Targets Database DAP000040 Link_out
PharmGKB PA451868 Link_out
IUPHAR 2406 Link_out
Guide to Pharmacology 2406 Link_out
Drug Product Database 2239769 Link_out
RxList http://www.rxlist.com/cgi/generic/verapsr.htm Link_out
Drugs.com http://www.drugs.com/verapamil.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Verapamil Link_out
ATC Codes
  • C08DA01
AHFS Codes
  • 24:28.92
PDB Entries Not Available
FDA label show (1.9 MB)
MSDS show (73.5 KB)
Interactions
Drug Interactions
Drug Interaction
Acebutolol Increased effect of both drugs
Amifostine Verapamil may enhance the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Verapamil should be withheld for 24 hours prior to Amifostine administration. Caution should be used at lower Amifostine doses used during radiotherapy, but routine interruption of Verapamil therapy is not recommended.
Aminophylline Verapamil increases the effect of theophylline
Amiodarone Additive bradycardic effects may occur. One case report of sinus arrest has been reported. Monitor for changes in the therapeutic effect and signs of Verapamil toxicity if Amiodarone is initiated, discontinued or dose changed.
Amobarbital Amobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Amobarbital is initiated, discontinued or dose changed.
Amprenavir Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Amprenavir is initiated, discontinued or dose changed.
Atazanavir Atazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Atazanavir is initiated, discontinued or dose changed.
Atenolol Increased effect of both drugs
Atorvastatin Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Atorvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce lovastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Atorvastatin if Verapamil is initiated, discontinued or dose changed.
Bisoprolol Increased effect of both drugs
Bromazepam Verapamil may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or a reductin in the bromazepam dose. Monitor for changes in the therapeutic and adverse effects of bromazepam if verapamil is initiated, discontinued or dose changed.
Buspirone Verapamil may increase the serum concentration of Buspirone. The likely occurs via Verapamil-mediated CYP3A4 inhibition resulting in decreased Buspirone metabolism. Monitor for changes in the therapeutic/adverse effects of Buspirone if Verpamil is initiated, discontinued or dose changed.
Butabarbital Butabarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Butabarbital is initiated, discontinued or dose changed.
Butalbital Butalbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Butalbital is initiated, discontinued or dose changed.
Carbamazepine Verapamil may increase the serum concentration of Carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic/adverse effects of Carbamazepine if Verapamil is initiated, discontinued or dose changed.
Carvedilol Increased effect of both drugs
Clarithromycin Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Clarithromycin is initiated, discontinued or dose changed.
Colchicine Verapamil may increase the serum concentration of Colchicine. This likely occurs via Verapamil-mediated inhibition of CYP3A4 and p-glycoprotein-mediated transport. Monitor for changes in the therapeutic/adverse effects of Colchicine if Verapamil is initiated, discontinued or dose changed.
Conivaptan Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Conivaptan is initiated, discontinued or dose changed.
Cyclosporine Verapamil may increase the serum concentration of cyclosporine by inhibiting CYP3A4-mediated metabolism of cyclosporine. Monitor for changes in the therapeutic/adverse effects of cyclosporine if verapamil is initiated, discontinued or dose changed.
Dabigatran etexilate Verapamil may increase serum concentrations of the active metabolite(s) of dabigatran etexilate, resulting in an increased risk of bleeding. It is also a strong p-glycoprotein inhibitor. Therapy modification should be considered.
Darunavir Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Darunavir is initiated, discontinued or dose changed.
Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Delavirdine is initiated, discontinued or dose changed.
Digitoxin Verapamil may increase the serum concentration of Digitoxin by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of Digitoxin if Verpamail is initiated, discontinued or dose changed.
Digoxin Verapamil may increase the serum concentration of Digoxin by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of Digoxin if Verpamail is initiated, discontinued or dose changed.
Dofetilide Verapamil may increase the plamsa levels of Dofetilide. Increased risk of torsade de pointes. Concomitant therapy is contraindicated.
Dronedarone Verapamil is a moderate CYP3A4 inhibitor and will increase dronedarone levels 1.4-1.7 fold. Decrease doses of non-dihyropyridinic calcium-channel blocker.
Eplerenone This CYP3A4 inhibitor increases the effect and toxicity of eplerenone
Erythromycin Erythromycin, a moderate CYP3A4 inhibitor, may increase the serum concentration of veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of verapamil if erythromycin is initiated, discontinued or dose changed.
Esmolol Increased effect of both drugs
Everolimus Concomitant administration may increase the serum concentrations of both agents. Concurrent use should be avoided.
Fluconazole Fluconazole may increase the serum concentration of Verapamil by decreasing Verapamil metabolism. This likely occurs via Fluconazole-mediated CYP3A4 inhibition. Monitor for changes in the therapeutic/adverse effects of Verapamil if Fluconazole is initiated, discontinued, or dose changed.
Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Fosamprenavir is initiated, discontinued or dose changed.
Halofantrine Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Halofantrine by decreasing its metabolism. Extreme caution with increased cardiac status monitoring should be used during concomitant therapy.
Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Imatinib is initiated, discontinued or dose changed.
Indinavir Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Indinavir is initiated, discontinued or dose changed.
Isoniazid Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Isoniazid is initiated, discontinued or dose changed.
Itraconazole Itraconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Itraconazole is initiated, discontinued or dose changed.
Ketoconazole Ketoconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Ketoconazole is initiated, discontinued or dose changed.
Labetalol Increased effect of both drugs
Lithium Signs of lithium toxicity
Lopinavir Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Lopinavir is initiated, discontinued or dose changed.
Lovastatin Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Lovastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce lovastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Lovastatin if Verapamil is initiated, discontinued or dose changed.
Methohexital Methohexital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Methohexital is initiated, discontinued or dose changed.
Methylphenobarbital Methylphenobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Methylphenobarbital is initiated, discontinued or dose changed.
Metoprolol Increased effect of both drugs
Miconazole Miconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Miconazole is initiated, discontinued or dose changed.
Midazolam Verapamil may increase the serum concentration of Midazolam by decreasing its metabolism. Avoid concomitant therapy if possible or consider a dose reduction in the initial dose of Midazolam.
Nadolol Increased effect of both drugs
Nafcillin Nafcillin may decrease the serum concentration of Verapamil by increasing its metabolism via CYP3A4. Monitor for changes in the therapeutic/adverse effects of Verapamil if Nafcillin is initiated, discontinued or dose changed.
Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Nefazodone is initiated, discontinued or dose changed.
Nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Nelfinavir is initiated, discontinued or dose changed.
Nicardipine Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Nicardipine is initiated, discontinued or dose changed.
Oxprenolol Increased effect of both drugs
Oxtriphylline Verapamil increases the effect of theophylline
Pentobarbital Pentobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Pentobarbital is initiated, discontinued or dose changed.
Phenobarbital Phenobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Phenobarbital is initiated, discontinued or dose changed.
Phenytoin Verapamil may increase the serum concentration of Phenytoin by decreasing its metabolism. Monitor for changes in the therapeutic/adverse effects of Phenytoin if Verapamil is initiated, discontinued or dose changed.
Pindolol Increased effect of both drugs
Posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Posaconazole is initiated, discontinued or dose changed.
Prazosin Risk of hypotension at the beginning of therapy
Primidone The barbiturate, primidone, decreases the effect of the calcium channel blocker, verapamil.
Propranolol Increased effect of both drugs
Quinidine Concurrent therapy may result in increased serum levels of both agents. Both agents are CYP3A4 inhibitors and substrates. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of the agent if the other is initiated, discontinued or dose changed.
Quinupristin This combination presents an increased risk of toxicity
Ranolazine Verapamil, a CYP3A4 inhibitor, may increase the serum concentration of Ranolazine. Concomitant therapy is contraindicated.
Rifabutin Rifabutin, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifabutin is initiated, discontinued or dose changed.
Rifampin Rifampin, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifampin is initiated, discontinued or dose changed.
Rifapentine Rifapentine, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifapentine is initiated, discontinued or dose changed.
Ritonavir Ritonavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Ritonavir is initiated, discontinued or dose changed.
Rituximab Verapamil may increase the hypotensive effects of Rituximab. Consider withholding Verapamil therapy for 12 hours prior to Rituximab infusion.
Saquinavir Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Saquinavir is initiated, discontinued or dose changed.
Secobarbital Secobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Secobarbital is initiated, discontinued or dose changed.
Silodosin Verapamil is a moderate inhibitor of CYP3A4 and inhibits P-glycoprotein thus increasing the potential for adverse effects
Simvastatin Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Simvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce Simvastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Simvastatin if Verapamil is initiated, discontinued or dose changed.
Tacrolimus The calcium channel blocker, Verapamil, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Verapamil therapy is initiated, discontinued or altered.
Tamsulosin Verapamil, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Verapamil is initiated, discontinued, or dose changed.
Telithromycin Telithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinblastine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Telithromycin is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Theophylline Verapamil increases the effect of theophylline
Thiopental Thiopental, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Thiopental is initiated, discontinued or dose changed.
Timolol Additive effects of decreased heart rate and contractility may occur. Increased risk of heart block.
Tipranavir Tipranavir, co-administered with Ritonavir, may alter the concentration of Verapamil. Monitor for efficacy and adverse/toxic effects of Verapamil.
Tolterodine Verapamil may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tolvaptan Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Tolvaptan. Concomitant therapy is contraindicated.
Topotecan The p-glycoprotein inhibitor, Verapamil, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Tramadol Verapamil may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inhibitor, Verapamil, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Verapamil is initiated, discontinued or dose changed.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Triazolam Verapamil may increase the serum concentration of Triazolam by decreasing its metabolism. Avoid concomitant therapy if possible or consider a dose reduction in the initial dose of Triazolam.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of verapamil by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of verapamil if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Avoid natural licorice.
  • Avoid taking with grapefruit juice.
  • Take with food.
Targets

1. Voltage-dependent L-type calcium channel subunit alpha-1C

Pharmacological action: yes
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the "high-voltage activated" (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds

Organism class: human
UniProt ID: Q13936 Link_out
Gene: CACNA1C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dilmac N, Hilliard N, Hockerman GH: Molecular determinants of frequency dependence and Ca2+ potentiation of verapamil block in the pore region of Cav1.2. Mol Pharmacol. 2004 Nov;66(5):1236-47. Epub 2004 Jul 30. Pubmed
  2. Morel N, Buryi V, Feron O, Gomez JP, Christen MO, Godfraind T: The action of calcium channel blockers on recombinant L-type calcium channel alpha1-subunits. Br J Pharmacol. 1998 Nov;125(5):1005-12. Pubmed
  3. Patel MK, Clunn GF, Lymn JS, Austin O, Hughes AD: Effect of serum withdrawal on the contribution of L-type calcium channels (CaV1.2) to intracellular Ca2+ responses and chemotaxis in cultured human vascular smooth muscle cells. Br J Pharmacol. 2005 Jul;145(6):811-7. Pubmed
  4. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

2. Voltage-dependent L-type calcium channel subunit alpha-1D

Pharmacological action: yes
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the "high-voltage activated" (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)

Organism class: human
UniProt ID: Q01668 Link_out
Gene: CACNA1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

3. Voltage-dependent L-type calcium channel subunit alpha-1F

Pharmacological action: yes
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the "high-voltage activated" (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)

Organism class: human
UniProt ID: O60840 Link_out
Gene: CACNA1F Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

4. Voltage-dependent L-type calcium channel subunit alpha-1S

Pharmacological action: yes
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the "high-voltage activated" (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle

Organism class: human
UniProt ID: Q13698 Link_out
Gene: CACNA1S Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

5. Voltage-dependent L-type calcium channel subunit beta-1

Pharmacological action: yes
Actions: inhibitor

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting

Organism class: human
UniProt ID: Q02641 Link_out
Gene: CACNB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

6. Voltage-dependent L-type calcium channel subunit beta-2

Pharmacological action: yes
Actions: inhibitor

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting

Organism class: human
UniProt ID: Q08289 Link_out
Gene: CACNB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

7. Voltage-dependent L-type calcium channel subunit beta-3

Pharmacological action: yes
Actions: inhibitor

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting

Organism class: human
UniProt ID: P54284 Link_out
Gene: CACNB3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

8. Voltage-dependent L-type calcium channel subunit beta-4

Pharmacological action: yes
Actions: inhibitor

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting

Organism class: human
UniProt ID: O00305 Link_out
Gene: CACNB4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

9. Voltage-dependent T-type calcium channel subunit alpha-1I

Pharmacological action: unknown
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. Isoform alpha-1I gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H

Organism class: human
UniProt ID: Q9P0X4 Link_out
Gene: CACNA1I Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

10. Voltage-dependent T-type calcium channel subunit alpha-1G

Pharmacological action: unknown
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes

Organism class: human
UniProt ID: O43497 Link_out
Gene: CACNA1G Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Freeze BS, McNulty MM, Hanck DA: State-dependent verapamil block of the cloned human Ca(v)3.1 T-type Ca(2+) channel. Mol Pharmacol. 2006 Aug;70(2):718-26. Epub 2006 May 12. Pubmed

11. Voltage-dependent N-type calcium channel subunit alpha-1B

Pharmacological action: unknown
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the "high-voltage activated" (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin- IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons

Organism class: human
UniProt ID: Q00975 Link_out
Gene: CACNA1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

12. Voltage-dependent P/Q-type calcium channel subunit alpha-1A

Pharmacological action: unknown
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the "high-voltage activated" (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin- IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA)

Organism class: human
UniProt ID: O00555 Link_out
Gene: CACNA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

13. Potassium voltage-gated channel subfamily H member 2

Pharmacological action: unknown
Actions: inhibitor

Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1

Organism class: human
UniProt ID: Q12809 Link_out
Gene: KCNH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Duan JJ, Ma JH, Zhang PH, Wang XP, Zou AR, Tu DN: Verapamil blocks HERG channel by the helix residue Y652 and F656 in the S6 transmembrane domain. Acta Pharmacol Sin. 2007 Jul;28(7):959-67. Pubmed
  2. Cheng HC, Incardona J, McCullough B: Isolated perfused and paced guinea pig heart to test for drug-induced changes of the QT interval. J Pharmacol Toxicol Methods. 2006 Nov-Dec;54(3):278-87. Epub 2006 Feb 28. Pubmed
  3. Schneider J, Hauser R, Andreas JO, Linz K, Jahnel U: Differential effects of human ether-a-go-go-related gene (HERG) blocking agents on QT duration variability in conscious dogs. Eur J Pharmacol. 2005 Apr 4;512(1):53-60. Pubmed
  4. Ridley JM, Dooley PC, Milnes JT, Witchel HJ, Hancox JC: Lidoflazine is a high affinity blocker of the HERG K(+)channel. J Mol Cell Cardiol. 2004 May;36(5):701-5. Pubmed
  5. Shimizu W, Aiba T, Antzelevitch C: Specific therapy based on the genotype and cellular mechanism in inherited cardiac arrhythmias. Long QT syndrome and Brugada syndrome. Curr Pharm Des. 2005;11(12):1561-72. Pubmed
  6. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

14. Sodium channel protein type 5 subunit alpha

Pharmacological action: unknown
Actions: other

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram

Organism class: human
UniProt ID: Q14524 Link_out
Gene: SCN5A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Milberg P, Reinsch N, Osada N, Wasmer K, Monnig G, Stypmann J, Breithardt G, Haverkamp W, Eckardt L: Verapamil prevents torsade de pointes by reduction of transmural dispersion of repolarization and suppression of early afterdepolarizations in an intact heart model of LQT3. Basic Res Cardiol. 2005 Jul;100(4):365-71. Epub 2005 Jun 10. Pubmed

15. ATP-sensitive inward rectifier potassium channel 11

Pharmacological action: unknown
Actions: inhibitor

This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium

Organism class: human
UniProt ID: Q14654 Link_out
Gene: KCNJ11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Yamada S, Kane GC, Behfar A, Liu XK, Dyer RB, Faustino RS, Miki T, Seino S, Terzic A: Protection conferred by myocardial ATP-sensitive K+ channels in pressure overload-induced congestive heart failure revealed in KCNJ11 Kir6.2-null mutant. J Physiol. 2006 Dec 15;577(Pt 3):1053-65. Epub 2006 Oct 12. Pubmed
  3. Shigeto M, Katsura M, Matsuda M, Ohkuma S, Kaku K: Nateglinide and mitiglinide, but not sulfonylureas, induce insulin secretion through a mechanism mediated by calcium release from endoplasmic reticulum. J Pharmacol Exp Ther. 2007 Jul;322(1):1-7. Epub 2007 Apr 4. Pubmed

16. Sodium-dependent serotonin transporter

Pharmacological action: unknown
Actions: other/unknown

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
  2. Brown NL, Sirugue O, Worcel M: The effects of some slow channel blocking drugs on high affinity serotonin uptake by rat brain synaptosomes. Eur J Pharmacol. 1986 Apr 9;123(1):161-5. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. Pubmed

2. Cytochrome P450 3A5

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A7

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 2C18

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P33260 Link_out
Gene: CYP2C18 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

9. Cytochrome P450 2B6

Actions: substrate, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

10. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate, inhibitor, inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Perloff MD, von Moltke LL, Fahey JM, Daily JP, Greenblatt DJ: Induction of P-glycoprotein expression by HIV protease inhibitors in cell culture. AIDS. 2000 Jun 16;14(9):1287-9. Pubmed
  2. Romiti N, Tramonti G, Chieli E: Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line. Toxicol Appl Pharmacol. 2002 Sep 1;183(2):83-91. Pubmed
  3. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. Pubmed
  4. Kawahara I, Kato Y, Suzuki H, Achira M, Ito K, Crespi CL, Sugiyama Y: Selective inhibition of human cytochrome P450 3A4 by N-[2®-hydroxy-1(S)-indanyl]-5-[2(S)-(1, 1-dimethylethylaminocarbonyl)-4-[(furo[2, 3-b]pyridin-5-yl)methyl]piperazin-1-yl]-4(S)-hydroxy-2®-phenylmethy lpentanamide and P-glycoprotein by valspodar in gene transfectant systems. Drug Metab Dispos. 2000 Oct;28(10):1238-43. Pubmed
  5. Fujita R, Ishikawa M, Takayanagi M, Takayanagi Y, Sasaki K: Enhancement of doxorubicin activity in multidrug-resistant cells by mefloquine. Methods Find Exp Clin Pharmacol. 2000 Jun;22(5):281-4. Pubmed
  6. Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. Pubmed
  7. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  8. Leonessa F, Kim JH, Ghiorghis A, Kulawiec RJ, Hammer C, Talebian A, Clarke R: C-7 analogues of progesterone as potent inhibitors of the P-glycoprotein efflux pump. J Med Chem. 2002 Jan 17;45(2):390-8. Pubmed
  9. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. Pubmed
  10. Zhang S, Morris ME: Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport. J Pharmacol Exp Ther. 2003 Mar;304(3):1258-67. Pubmed
  11. Horie K, Tang F, Borchardt RT: Isolation and characterization of Caco-2 subclones expressing high levels of multidrug resistance protein efflux transporter. Pharm Res. 2003 Feb;20(2):161-8. Pubmed
  12. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. Pubmed
  13. van der Sandt IC, Blom-Roosemalen MC, de Boer AG, Breimer DD: Specificity of doxorubicin versus rhodamine-123 in assessing P-glycoprotein functionality in the LLC-PK1, LLC-PK1:MDR1 and Caco-2 cell lines. Eur J Pharm Sci. 2000 Sep;11(3):207-14. Pubmed
  14. Ibrahim S, Peggins J, Knapton A, Licht T, Aszalos A: Influence of antipsychotic, antiemetic, and Ca(2+) channel blocker drugs on the cellular accumulation of the anticancer drug daunorubicin: P-glycoprotein modulation. J Pharmacol Exp Ther. 2000 Dec;295(3):1276-83. Pubmed
  15. Wang EJ, Casciano CN, Clement RP, Johnson WW: Evaluation of the interaction of loratadine and desloratadine with P-glycoprotein. Drug Metab Dispos. 2001 Aug;29(8):1080-3. Pubmed
  16. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE: Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003 Apr;305(1):197-204. Pubmed
  17. Wils P, Phung-Ba V, Warnery A, Lechardeur D, Raeissi S, Hidalgo IJ, Scherman D: Polarized transport of docetaxel and vinblastine mediated by P-glycoprotein in human intestinal epithelial cell monolayers. Biochem Pharmacol. 1994 Oct 7;48(7):1528-30. Pubmed
  18. Hait WN, Gesmonde JF, Murren JR, Yang JM, Chen HX, Reiss M: Terfenadine (Seldane): a new drug for restoring sensitivity to multidrug resistant cancer cells. Biochem Pharmacol. 1993 Jan 26;45(2):401-6. Pubmed
  19. Pouliot JF, L’Heureux F, Liu Z, Prichard RK, Georges E: Reversal of P-glycoprotein-associated multidrug resistance by ivermectin. Biochem Pharmacol. 1997 Jan 10;53(1):17-25. Pubmed
  20. Kuhnel JM, Perrot JY, Faussat AM, Marie JP, Schwaller MA: Functional assay of multidrug resistant cells using JC-1, a carbocyanine fluorescent probe. Leukemia. 1997 Jul;11(7):1147-55. Pubmed
  21. Kim AE, Dintaman JM, Waddell DS, Silverman JA: Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther. 1998 Sep;286(3):1439-45. Pubmed
  22. Bebawy M, Morris MB, Roufogalis BD: A continuous fluorescence assay for the study of P-glycoprotein-mediated drug efflux using inside-out membrane vesicles. Anal Biochem. 1999 Mar 15;268(2):270-7. Pubmed
  23. Golstein PE, Boom A, van Geffel J, Jacobs P, Masereel B, Beauwens R: P-glycoprotein inhibition by glibenclamide and related compounds. Pflugers Arch. 1999 Apr;437(5):652-60. Pubmed
  24. Jonsson O, Behnam-Motlagh P, Persson M, Henriksson R, Grankvist K: Increase in doxorubicin cytotoxicity by carvedilol inhibition of P-glycoprotein activity. Biochem Pharmacol. 1999 Dec 1;58(11):1801-6. Pubmed
  25. Eagling VA, Profit L, Back DJ: Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999 Oct;48(4):543-52. Pubmed
  26. Choi CH, Kim JH, Kim SH: Reversal of P-glycoprotein-mediated MDR by 5,7,3’,4’,5’-pentamethoxyflavone and SAR. Biochem Biophys Res Commun. 2004 Jul 30;320(3):672-9. Pubmed
  27. Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br J Pharmacol. 2004 Dec;143(7):856-64. Epub 2004 Oct 25. Pubmed
  28. Hu K, Morris ME: Effects of benzyl-, phenethyl-, and alpha-naphthyl isothiocyanates on P-glycoprotein- and MRP1-mediated transport. J Pharm Sci. 2004 Jul;93(7):1901-11. Pubmed
  29. Lee BH, Lee CO, Kwon MJ, Yi KY, Yoo SE, Choi SU: Differential effects of the optical isomers of KR30031 on cardiotoxicity and on multidrug resistance reversal activity. Anticancer Drugs. 2003 Feb;14(2):175-81. Pubmed
  30. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. Pubmed
  31. Petri N, Tannergren C, Rungstad D, Lennernas H: Transport characteristics of fexofenadine in the Caco-2 cell model. Pharm Res. 2004 Aug;21(8):1398-404. Pubmed
  32. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. Pubmed
  33. Santoni-Rugiu E, Silverman JA: Functional characterization of the rat mdr1b encoded P-glycoprotein: not all inducing agents are substrates. Carcinogenesis. 1997 Nov;18(11):2255-63. Pubmed
  34. Sieczkowski E, Lehner C, Ambros PF, Hohenegger M: Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. Int J Cancer. 2010 May 1;126(9):2025-35. Pubmed
  35. Chiu LY, Ko JL, Lee YJ, Yang TY, Tee YT, Sheu GT: L-type calcium channel blockers reverse docetaxel and vincristine-induced multidrug resistance independent of ABCB1 expression in human lung cancer cell lines. Toxicol Lett. 2010 Feb 15;192(3):408-18. Epub 2009 Nov 26. Pubmed
  36. Karlsson JE, Heddle C, Rozkov A, Rotticci-Mulder J, Tuvesson O, Hilgendorf C, Andersson TB: High-activity p-glycoprotein, multidrug resistance protein 2, and breast cancer resistance protein membrane vesicles prepared from transiently transfected human embryonic kidney 293-epstein-barr virus nuclear antigen cells. Drug Metab Dispos. 2010 Apr;38(4):705-14. Epub 2010 Jan 13. Pubmed
  37. Jutabha P, Wempe MF, Anzai N, Otomo J, Kadota T, Endou H: Xenopus laevis oocytes expressing human P-glycoprotein: probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux. Pharmacol Res. 2010 Jan;61(1):76-84. Epub 2009 Jul 21. Pubmed
  38. Kugawa F, Suzuki T, Miyata M, Tomono K, Tamanoi F: Construction of a model cell line for the assay of MDR1 (multi drug resistance gene-1) substrates/inhibitors using HeLa cells. Pharmazie. 2009 May;64(5):296-300. Pubmed
  39. Dahan A, Amidon GL: Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7. Epub 2009 Jun 18. Pubmed
  40. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. Epub 2009 May 12. Pubmed
  41. Dahan A, Sabit H, Amidon GL: The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport. AAPS J. 2009 Jun;11(2):205-13. Epub 2009 Mar 25. Pubmed
  42. Pauli-Magnus C, von Richter O, Burk O, Ziegler A, Mettang T, Eichelbaum M, Fromm MF: Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein. J Pharmacol Exp Ther. 2000 May;293(2):376-82. Pubmed
  43. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed
  44. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. Pubmed
  45. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. Pubmed
  46. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed
  47. Dagenais C, Graff CL, Pollack GM: Variable modulation of opioid brain uptake by P-glycoprotein in mice. Biochem Pharmacol. 2004 Jan 15;67(2):269-76. Pubmed
  48. Borgnia MJ, Eytan GD, Assaraf YG: Competition of hydrophobic peptides, cytotoxic drugs, and chemosensitizers on a common P-glycoprotein pharmacophore as revealed by its ATPase activity. J Biol Chem. 1996 Feb 9;271(6):3163-71. Pubmed
  49. Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. Pubmed
  50. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. Pubmed

2. Solute carrier family 22 member 1

Actions: inhibitor

Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

UniProt ID: O15245 Link_out
Gene: SLC22A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. Pubmed
  2. Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. Pubmed

3. Canalicular multispecific organic anion transporter 2

Actions: inhibitor

May act as an inducible transporter in the biliary and intestinal excretion of organic anions

UniProt ID: O15438 Link_out
Gene: ABCC3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. Pubmed

4. Multidrug resistance-associated protein 4

Actions: inhibitor

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. Pubmed
  2. Bai J, Lai L, Yeo HC, Goh BC, Tan TM: Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57. Pubmed

5. Organic cation/carnitine transporter 2

Actions: inhibitor

Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also Relative uptake activity ratio of carnitine to TEA is 11.3

UniProt ID: O76082 Link_out
Gene: SLC22A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed
  2. Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. Pubmed

6. Bile salt export pump

Actions: inhibitor

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. Pubmed

7. Multidrug resistance-associated protein 1

Actions: inhibitor

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lespine A, Dupuy J, Orlowski S, Nagy T, Glavinas H, Krajcsi P, Alvinerie M: Interaction of ivermectin with multidrug resistance proteins (MRP1, 2 and 3). Chem Biol Interact. 2006 Feb 25;159(3):169-79. Epub 2005 Dec 27. Pubmed

8. Solute carrier organic anion transporter family member 1A2

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out
Gene: SLCO1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. Pubmed
  2. Shitara Y, Sugiyama D, Kusuhara H, Kato Y, Abe T, Meier PJ, Itoh T, Sugiyama Y: Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm Res. 2002 Feb;19(2):147-53. Pubmed

9. Multidrug resistance-associated protein 7

Actions: inhibitor

ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion

UniProt ID: Q5T3U5 Link_out
Gene: ABCC10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. Pubmed

10. Canalicular multispecific organic anion transporter 1

Actions: inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. Pubmed

11. Organic cation/carnitine transporter 1

Actions: inhibitor

Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET)

UniProt ID: Q9H015 Link_out
Gene: SLC22A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. Pubmed
  2. Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V: Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta. 2000 Jun 1;1466(1-2):315-27. Pubmed

12. ATP-binding cassette sub-family G member 2

Actions: inhibitor

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ozvegy-Laczka C, Hegedus T, Varady G, Ujhelly O, Schuetz JD, Varadi A, Keri G, Orfi L, Nemet K, Sarkadi B: High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol. 2004 Jun;65(6):1485-95. Pubmed

13. Solute carrier organic anion transporter family member 1B1

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Oostendorp RL, van de Steeg E, van der Kruijssen CM, Beijnen JH, Kenworthy KE, Schinkel AH, Schellens JH: Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors. Drug Metab Dispos. 2009 Apr;37(4):917-23. Epub 2009 Jan 12. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19