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Identification
Name Nicardipine
Accession Number DB00622 (APRD00088)
Type small molecule
Groups approved
Description

A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Nicardipine HCl
  • Nicardipino [INN-Spanish]
  • Nicardipinum [INN-Latin]
Synonyms
Nicardipine HCl
Nicardipino [INN-Spanish]
Nicardipinum [INN-Latin]
Salts Not Available
Brand names
Name Company
Cardene Roche
Cardene IV ESP Pharma
Cardene SR Roche
Brand mixtures Not Available
Categories
  • Antihypertensive Agents
  • Vasodilator Agents
  • Antiarrhythmic Agents
  • Calcium Channel Blockers
  • Dihydropyridines
CAS number 55985-32-5
Weight Average: 479.525
Monoisotopic: 479.205635675
Chemical Formula C26H29N3O6
InChI Key InChIKey=ZBBHBTPTTSWHBA-UHFFFAOYSA-N
InChI
InChI=1S/C26H29N3O6/c1-17-22(25(30)34-4)24(20-11-8-12-21(15-20)29(32)33)23(18(2)27-17)26(31)35-14-13-28(3)16-19-9-6-5-7-10-19/h5-12,15,24,27H,13-14,16H2,1-4H3
Plain Text
IUPAC Name
3-{2-[benzyl(methyl)amino]ethyl} 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OCCN(C)CC1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Nitrobenzenes
Substructures
  • Dihydropyridines
  • Carboxylic Acids and Derivatives
  • Nitrobenzenes
  • Acetates
  • Oxoazaniums
  • Ethers
  • Benzene and Derivatives
  • Nitro compounds
  • Enamines
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
Pharmacology
Indication Used for the management of patients with chronic stable angina and for the treatment of hypertension.
Pharmacodynamics Nicardipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nicardipine is similar to other peripheral vasodilators. Nicardipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Mechanism of action By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, nicardipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Absorption While nicardipine is completely absorbed, it is subject to saturable first pass metabolism and the systemic bioavailability is about 35% following a 30 mg oral dose at steady state.
Volume of distribution
  • 8.3 L/kg
Protein binding >95%
Metabolism Nicardipine HCl is metabolized extensively by the liver.
Route of elimination Nicardipine has been shown to be rapidly and extensively metabolized by the liver.
Half life 8.6 hours
Clearance
  • 0.4 L/hr∙kg [Following infusion]
Toxicity Oral LD50 Rat = 184 mg/kg, Oral LD50 Mouse = 322 mg/kg
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ekr therapeutics inc
  • Amneal pharmaceutical
  • Barr laboratories inc
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Bedford laboratories div ben venue laboratories inc
  • Bioniche pharma usa llc
  • Exela pharma sciences
  • Navinta llc
  • Pharmaforce inc
  • Sun pharma global inc
  • Wockhardt ltd
Packagers
Dosage forms
Form Route Strength
Capsule Oral 20 mg
Capsule Oral 30 mg
Capsule, extended release Oral 30 mg
Capsule, extended release Oral 45 mg
Capsule, extended release Oral 60 mg
Injection, solution, concentrate Intravenous 2.5 mg/ml
Prices
Unit description Cost Unit
Cardene SR 60 60 mg 12 Hour Capsule Bottle 142.91 USD bottle
Nicardipine 25 mg/10 ml ampule 25.01 USD ml
Nicardipine 25 mg/10 ml vial 10.42 USD ml
Cardene SR 45 mg 12 Hour Capsule 3.22 USD capsule
Cardene sr 45 mg capsule 2.9 USD capsule
Cardene sr 60 mg capsule sa 2.29 USD capsule
Cardene SR 30 mg 12 Hour Capsule 2.02 USD capsule
Cardene sr 45 mg capsule sa 1.91 USD capsule
Cardene-dex 40 mg/200 ml iv 1.35 USD ml
Cardene-nacl 40 mg/200 ml iv 1.35 USD ml
Cardene 30 mg capsule 1.28 USD capsule
Cardene sr 30 mg capsule sa 1.21 USD capsule
Cardene sr 30 mg capsule 0.87 USD capsule
Cardene 20 mg capsule 0.8 USD capsule
NiCARdipine HCl 30 mg capsule 0.68 USD capsule
Cardene-dex 20 mg/200 ml soln 0.67 USD ml
Cardene-nacl 20 mg/200 ml soln 0.67 USD ml
Nicardipine 30 mg capsule 0.66 USD capsule
NiCARdipine HCl 20 mg capsule 0.48 USD capsule
Nicardipine 20 mg capsule 0.46 USD capsule
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Patents
Country Patent Number Approved Expires (estimated)
United States 7612102 2007-12-26 2027-12-26
United States 5164405 1992-11-17 2009-11-17
Properties
State solid
Melting point 136-138 oC
Experimental Properties
Property Value Source
water solubility 2.2 mg/L PhysProp
logP 3.6 PhysProp
Predicted Properties
Property Value Source
water solubility 2.47e-03 g/l ALOGPS
logP 4.34 ALOGPS
logP 3.56 ChemAxon Molconvert
logS -5.3 ALOGPS
pKa 0 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 113.69 ChemAxon Molconvert
rotatable bond count 11 ChemAxon Molconvert
refractivity 134.8 ChemAxon Molconvert
polarizability 49.95 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07264 Link_out
PubChem Compound 4474 Link_out
PubChem Substance 46504482 Link_out
ChemSpider 4319 Link_out
BindingDB 50017085 Link_out
Therapeutic Targets Database DAP000486 Link_out
PharmGKB PA450620 Link_out
IUPHAR 2559 Link_out
Guide to Pharmacology 2559 Link_out
Drug Product Database 2162733 Link_out
RxList http://www.rxlist.com/cgi/generic/nicardipine.htm Link_out
Drugs.com http://www.drugs.com/cdi/nicardipine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Nicardipine Link_out
ATC Codes
  • C08CA04
AHFS Codes
  • 24:28.08
PDB Entries Not Available
FDA label show (1.26 MB)
MSDS show (106 KB)
Interactions
Drug Interactions
Drug Interaction
Bromazepam Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if nicardipine is initiated, discontinued or dose changed. Dosage adjustments may be required.
Cyclosporine Nicardipine increases the effect and toxicity of cyclosporine
Dantrolene Nicardipine may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if nicardipine is initiated, discontinued or dose changed.
Quinupristin This combination presents an increased risk of toxicity
Tacrolimus The calcium channel blocker, Nicardipine, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nicardipine therapy is initiated, discontinued or altered.
Tadalafil Nicardipine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamoxifen Nicardipine may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Nicardipine may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Nicardipine is initiated, discontinued or dose changed.
Tamsulosin Nicardipine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nicardipine is initiated, discontinued, or dose changed.
Telithromycin Co-administration may result in altered plasma concentrations of Nicardipine and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
Temsirolimus Nicardipine may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Teniposide The strong CYP3A4 inhibitor, Nicardipine, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Nicardipine is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thiopental The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nicardipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nicardipine if Thiopental is initiated, discontinued or dose changed.
Tiagabine The strong CYP3A4 inhibitor, Nicardipine, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Nicardipine is initiated, discontinued or dose changed.
Tipranavir Tipranavir, co-administered with Ritonavir, may alter the concentration of Nicardipine. Monitor for efficacy and adverse/toxic effects of Nicardipine.
Tolbutamide Nicardipine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Nicardipine is initiated, discontinued or dose changed.
Tolterodine Nicardipine may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Topotecan The p-glycoprotein inhibitor, Nicardipine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Torasemide Nicardipine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Nicardipine is initiated, discontinued or dose changed.
Tramadol Nicardipine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Nicardipine may decrease the effect of Tramadol by decreasing active metabolite production.
Trazodone The CYP3A4 inhibitor, Nicardipine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Nicardipine is initiated, discontinued or dose changed.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Trimethoprim The strong CYP2C9 inhibitor, Nicardipine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Nicardipine is initiated, discontinued or dose changed.
Trimipramine The strong CYP3A4 inhibitor, Nicardipine, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Nicardipine is initiated, discontinued or dose changed.
Vardenafil Nicardipine, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Venlafaxine Nicardipine, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Nicardipine is initiated, discontinued, or dose changed.
Verapamil 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.
Vinblastine Nicardipine, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Nicardipine is initiated, discontinued or dose changed.
Vincristine Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nicardipine is initiated, discontinued or dose changed.
Vinorelbine Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Nicardipine is initiated, discontinued or dose changed.
Voriconazole Nicardipine, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of nicardipine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole and nicardipine if concomitant therapy is initiated, discontinued or doses are changed.
Warfarin Nicardipine, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if nicardipine is initiated, discontinued or dose changed.
Zafirlukast Nicardipine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if nicardipine is initiated, discontinued or dose changed.
Zolpidem Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if nicardipine is initiated, discontinued or dose changed.
Zonisamide Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if nicardipine is initiated, discontinued or dose changed.
Zopiclone Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if nicardipine is initiated, discontinued or dose changed.
Food Interactions
  • Grapefruit and grapefruit juice should be avoided throughout treatment. Grapefruit can increase serum levels of this product.
  • Take without regard to meals.
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Striessnig, J. (2004). Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin, Germany: Springer.

2. 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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Striessnig, J. (2004). Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin, Germany: Springer.

3. 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. Bell DC, Butcher AJ, Berrow NS, Page KM, Brust PF, Nesterova A, Stauderman KA, Seabrook GR, Nurnberg B, Dolphin AC: Biophysical properties, pharmacology, and modulation of human, neuronal L-type (alpha(1D), Ca(V)1.3) voltage-dependent calcium currents. J Neurophysiol. 2001 Feb;85(2):816-27. Pubmed

4. Voltage-dependent calcium channel subunit alpha-2/delta-1

Pharmacological action: yes
Actions: inhibitor

Calcium channel protein which plays an important role in excitation-contraction coupling

Organism class: human
UniProt ID: P54289 Link_out
Gene: CACNA2D1 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. Striessnig, J. (2004). Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin, Germany: Springer.

5. Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A

Pharmacological action: unknown
Actions: inhibitor

Has a higher affinity for cGMP than for cAMP

Organism class: human
UniProt ID: P54750 Link_out
Gene: PDE1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. Pubmed

6. Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B

Pharmacological action: unknown
Actions: inhibitor

Has a preference for cGMP as a substrate

Organism class: human
UniProt ID: Q01064 Link_out
Gene: PDE1B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. Pubmed

7. Alpha-1A adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thayer SA, Welcome M, Chhabra A, Fairhurst AS: Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors. Biochem Pharmacol. 1985 Jan 15;34(2):175-80. Pubmed

8. Alpha-1B adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thayer SA, Welcome M, Chhabra A, Fairhurst AS: Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors. Biochem Pharmacol. 1985 Jan 15;34(2):175-80. Pubmed

9. Alpha-1D adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium

Organism class: human
UniProt ID: P25100 Link_out
Gene: ADRA1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thayer SA, Welcome M, Chhabra A, Fairhurst AS: Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors. Biochem Pharmacol. 1985 Jan 15;34(2):175-80. Pubmed

10. Muscarinic acetylcholine receptor M1

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P11229 Link_out
Gene: CHRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thayer SA, Welcome M, Chhabra A, Fairhurst AS: Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors. Biochem Pharmacol. 1985 Jan 15;34(2):175-80. Pubmed

11. Muscarinic acetylcholine receptor M2

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition

Organism class: human
UniProt ID: P08172 Link_out
Gene: CHRM2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thayer SA, Welcome M, Chhabra A, Fairhurst AS: Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors. Biochem Pharmacol. 1985 Jan 15;34(2):175-80. Pubmed

12. Muscarinic acetylcholine receptor M3

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P20309 Link_out
Gene: CHRM3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thayer SA, Welcome M, Chhabra A, Fairhurst AS: Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors. Biochem Pharmacol. 1985 Jan 15;34(2):175-80. Pubmed

13. Muscarinic acetylcholine receptor M4

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase

Organism class: human
UniProt ID: P08173 Link_out
Gene: CHRM4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thayer SA, Welcome M, Chhabra A, Fairhurst AS: Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors. Biochem Pharmacol. 1985 Jan 15;34(2):175-80. Pubmed

14. Muscarinic acetylcholine receptor M5

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P08912 Link_out
Gene: CHRM5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thayer SA, Welcome M, Chhabra A, Fairhurst AS: Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors. Biochem Pharmacol. 1985 Jan 15;34(2):175-80. Pubmed

15. Calmodulin

Pharmacological action: unknown
Actions: other/unknown

Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases

Organism class: human
UniProt ID: P62158 Link_out
Gene: CALM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thayer SA, Fairhurst AS: The interaction of dihydropyridine calcium channel blockers with calmodulin and calmodulin inhibitors. Mol Pharmacol. 1983 Jul;24(1):6-9. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor, 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 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. 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

2. Cytochrome P450 2D6

Actions: substrate, 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

3. Cytochrome P450 2C9

Actions: inhibitor, 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. 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. 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 2C19

Actions: inhibitor

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

5. Cytochrome P450 2C8

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. 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. 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 2B6

Actions: 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

7. Cytochrome P450 2E1

Actions: substrate

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 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 3A5

Actions: 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. 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

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. Katoh M, Nakajima M, Yamazaki H, Yokoi T: Inhibitory potencies of 1,4-dihydropyridine calcium antagonists to P-glycoprotein-mediated transport: comparison with the effects on CYP3A4. Pharm Res. 2000 Oct;17(10):1189-97. Pubmed
  2. Lentz KA, Polli JW, Wring SA, Humphreys JE, Polli JE: Influence of passive permeability on apparent P-glycoprotein kinetics. Pharm Res. 2000 Dec;17(12):1456-60. Pubmed
  3. 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
  4. Takara K, Sakaeda T, Tanigawara Y, Nishiguchi K, Ohmoto N, Horinouchi M, Komada F, Ohnishi N, Yokoyama T, Okumura K: Effects of 12 Ca2+ antagonists on multidrug resistance, MDR1-mediated transport and MDR1 mRNA expression. Eur J Pharm Sci. 2002 Aug;16(3):159-65. Pubmed
  5. 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
  6. 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
  7. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 14, 2012 11:43