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Identification
Name Amlodipine
Accession Number DB00381 (APRD00520)
Type small molecule
Groups approved
Description

Amlodipine is a long-acting 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, amlodipine prevents calcium-dependent myocyte contraction and vasoconstriction. A second proposed mechanism for the drug’s vasodilatory effects involves pH-dependent inhibition of calcium influx via inhibition of smooth muscle carbonic anhydrase. Some studies have shown that amlodipine also exerts inhibitory effects on voltage-gated N-type calcium channels. N-type calcium channels located in the central nervous system may be involved in nociceptive signaling and pain sensation. Amlodipine is used to treat hypertension and chronic stable angina.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Amlodipine Benzenesulfonate
Amlodipine Besilate
Amlodipine Besylate
Amlodipine Free Base
Amlodipino [Spanish]
Amlodipinum [Latin]
Salts Not Available
Brand names
Name Company
Amlocard AWD (Germany)
Amlodis Eczacibasi (Turkey)
Amvaz Reddy (Malaysia)
Coroval Sandoz (Argentina)
Lipinox
Lotrel
Norvasc Pfizer
Brand mixtures
Brand Name Ingredients
Azor amlodipine + olmesartan
Caduet amlodipine + atorvastatin
Coroval B amlodipine + benazepril
Exforge amlodipine + valsartan
Lotrel amlodipine + benazepril
Categories
  • Antihypertensive Agents
  • Vasodilator Agents
  • Calcium Channel Blockers
  • Antianginals
CAS number 88150-42-9
Weight Average: 408.876
Monoisotopic: 408.145199627
Chemical Formula C20H25ClN2O5
InChI Key InChIKey=HTIQEAQVCYTUBX-UHFFFAOYSA-N
InChI
InChI=1S/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3
Plain Text
IUPAC Name
3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
CCOC(=O)C1=C(COCCN)NC(C)=C(C1C1=CC=CC=C1Cl)C(=O)OC
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Dihydropyridines
  • Carboxylic Acids and Derivatives
  • Benzene and Derivatives
  • Halobenzenes
Substructures
  • Dihydropyridines
  • Carboxylic Acids and Derivatives
  • Acetates
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Enamines
  • Heterocyclic compounds
  • Aromatic compounds
Pharmacology
Indication For the treatment of hypertension and chronic stable angina.
Pharmacodynamics Amlodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that DHP CCBs target L-type calcium channels, the major channel in muscle cells that mediate contraction; however, some studies have indicated that amlodipine also binds to and inhibits N-type calcium channels (see references in Targets section). Similar to other DHP CCBs, amlodipine binds directly to inactive L-type calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives amlodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, amlodipine has little effect on cardiac myocytes and conduction cells.
Mechanism of action Amlodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of amlodipine result in an overall decrease in blood pressure. Amlodipine is a long-acting CCB that may be used to treat mild to moderate essential hypertension and exertion-related angina (chronic stable angina). Another possible mechanism is that amlodipine inhibits vascular smooth muscle carbonic anhydrase I activity causing cellular pH increases which may be involved in regulating intracelluar calcium influx through calcium channels.
Absorption Amlodipine is slowly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached 6-12 hour following oral administration. Its estimated bioavailability is 64-90%. Absorption is not affected by food.
Volume of distribution Not Available
Protein binding 97.5%
Metabolism Hepatic. Metabolized extensively (90%) to inactive metabolites via the cytochrome P450 3A4 isozyme.
Route of elimination Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine.
Half life 30-50 hours
Clearance Not Available
Toxicity Gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to an including shock with fatal outcome have been reported.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00376 Amlodipine Pathway SMP00376
Pharmacoeconomics
Manufacturers
  • Synthon pharmaceuticals inc
  • Actavis totowa llc
  • Alkem laboratories ltd
  • Amneal pharmaceuticals ny llc
  • Apotex inc
  • Aurobindo pharma ltd
  • Caraco pharmaceutical laboratories ltd
  • Dr reddys laboratories ltd
  • Gedeon richter usa inc
  • Genpharm inc
  • Glenmark generics ltd
  • Invagen pharmaceuticals inc
  • Lek pharmaceuticals dd
  • Lupin ltd
  • Matrix laboratories ltd
  • Mutual pharmacal co
  • Mylan laboratories inc
  • Orchid healthcare
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Teva pharmaceuticals usa inc
  • Torrent pharmaceuticals ltd
  • Upsher smith laboratories inc
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
  • Wockhardt ltd
  • World gen llc
  • Zydus pharmaceuticals usa inc
  • Pfizer inc
  • Dr reddys laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral 10 mg
Tablet Oral 2.5 mg
Tablet Oral 5 mg
Prices
Unit description Cost Unit
Amlodipine besylate powder 9.99 USD g
Lotrel 10-40 mg capsule 5.21 USD capsule
Lotrel 10-20 mg capsule 4.8 USD capsule
Lotrel 5-40 mg capsule 4.37 USD capsule
Lotrel 5-20 mg capsule 4.13 USD capsule
Lotrel 5-10 mg capsule 3.91 USD capsule
Lotrel 2.5-10 mg capsule 3.83 USD capsule
Norvasc 10 mg tablet 3.16 USD tablet
Amlodipine besylate 10 mg tablet 2.42 USD tablet
Norvasc 2.5 mg tablet 2.36 USD tablet
Norvasc 5 mg tablet 2.36 USD tablet
Norvasc 10 mg Tablet 2.14 USD tablet
Amlodipine besylate 2.5 mg tablet 1.76 USD tablet
Amlodipine besylate 5 mg tablet 1.76 USD tablet
Norvasc 5 mg Tablet 1.44 USD tablet
Amlodipine 10 mg Tablet 1.03 USD tablet
Apo-Amlodipine 10 mg Tablet 1.03 USD tablet
Co Amlodipine 10 mg Tablet 1.03 USD tablet
Gd-Amlodipine 10 mg Tablet 1.03 USD tablet
Jamp-Amlodipine 10 mg Tablet 1.03 USD tablet
Mylan-Amlodipine 10 mg Tablet 1.03 USD tablet
Novo-Amlodipine 10 mg Tablet 1.03 USD tablet
Phl-Amlodipine 10 mg Tablet 1.03 USD tablet
Pms-Amlodipine 10 mg Tablet 1.03 USD tablet
Ran-Amlodipine 10 mg Tablet 1.03 USD tablet
Ratio-Amlodipine 10 mg Tablet 1.03 USD tablet
Sandoz Amlodipine 10 mg Tablet 1.03 USD tablet
Amlodipine 5 mg Tablet 0.7 USD tablet
Apo-Amlodipine 5 mg Tablet 0.7 USD tablet
Co Amlodipine 5 mg Tablet 0.7 USD tablet
Gd-Amlodipine 5 mg Tablet 0.7 USD tablet
Jamp-Amlodipine 5 mg Tablet 0.7 USD tablet
Mylan-Amlodipine 5 mg Tablet 0.7 USD tablet
Novo-Amlodipine 5 mg Tablet 0.7 USD tablet
Phl-Amlodipine 5 mg Tablet 0.7 USD tablet
Pms-Amlodipine 5 mg Tablet 0.7 USD tablet
Ran-Amlodipine 5 mg Tablet 0.7 USD tablet
Ratio-Amlodipine 5 mg Tablet 0.7 USD tablet
Sandoz Amlodipine 5 mg Tablet 0.7 USD tablet
Phl-Amlodipine 2.5 mg Tablet 0.35 USD tablet
Pms-Amlodipine 2.5 mg Tablet 0.35 USD tablet
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Patents
Country Patent Number Approved Expires (estimated)
United States 6828339 2002-11-20 2022-11-20
Canada 2170278 1999-08-03 2014-08-10
Properties
State solid
Experimental Properties
Property Value Source
melting point 178-179 °C Not Available
water solubility 75.3 mg/L Not Available
logP 3.00 AUSTIN,RP ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 7.40e-03 g/l ALOGPS
logP 2.22 ALOGPS
logP 1.64 ChemAxon
logS -4.7 ALOGPS
pKa (strongest basic) 9.45 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 99.88 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 108.64 ChemAxon
polarizability 42.29 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Nayler WG, Gu XH: The unique binding properties of amlodipine: a long-acting calcium antagonist. J Hum Hypertens. 1991 Aug;5 Suppl 1:55-9. Pubmed
  2. van Zwieten PA: Amlodipine: an overview of its pharmacodynamic and pharmacokinetic properties. Clin Cardiol. 1994 Sep;17(9 Suppl 3):III3-6. Pubmed
External Links
Resource Link
KEGG Compound C06825 Link_out
PubChem Compound 2162 Link_out
PubChem Substance 46507214 Link_out
ChemSpider 2077 Link_out
ChEBI 2668 Link_out
ChEMBL 2668 Link_out
Therapeutic Targets Database DAP000139 Link_out
PharmGKB PA448388 Link_out
Drug Product Database 878936 Link_out
RxList http://www.rxlist.com/cgi/generic/amlod2.htm Link_out
Drugs.com http://www.drugs.com/amlodipine.html Link_out
PDRhealth http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=nor1306.html&contentName=Norvasc&contentId=538 Link_out
Wikipedia http://en.wikipedia.org/wiki/Amlodipine Link_out
ATC Codes
  • C08CA01
AHFS Codes
  • 24:28.08
PDB Entries
FDA label show (91.4 KB)
MSDS show (74.5 KB)
Interactions
Drug Interactions
Drug Interaction
Diltiazem Diltiazem may increase the serum concentration of amlodipine. Concomitant therapy will result in additive hypotensive effects. Monitor for changes in the hypotensive effect of amlodipine if diltiazem is initiated, discontinued or dose changed.
Quinupristin This combination presents an increased risk of toxicity
Tacrine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Amlopidine, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Amlopidine is initiated, discontinued or if the dose is changed.
Telaprevir Telaprevir inhibits the metabolism of amlodipine and concomitant therapy is contraindicated.
Telithromycin Telithromycin may reduce clearance of Amlopidine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Amlopidine if Telithromycin is initiated, discontinued or dose changed.
Thiopental The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Amlodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Amlodipine if Thiopental is initiated, discontinued or dose changed.
Tipranavir Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Amlopidine. Monitor for changes in Amlopidine therapeutic and toxic effects if Tipranavir is initiated, discontinued or dose changed.
Tizanidine Amlopidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Voriconazole Voriconazole may increase the serum concentration of amlodipine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amlodipine if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Avoid natural licorice.
  • Grapefruit down regulates post-translational expression of CYP3A4, the major metabolizing enzyme of amlodipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of amlodipine and may cause toxicity. Avoid grapefruit products while on this medication.
  • 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 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.

3. 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.

4. 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. Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. Epub 2008 Nov 24. Pubmed

5. 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. Peterson BZ, Catterall WA: Allosteric interactions required for high-affinity binding of dihydropyridine antagonists to Ca(V)1.1 Channels are modulated by calcium in the pore. Mol Pharmacol. 2006 Aug;70(2):667-75. Epub 2006 May 4. Pubmed

6. 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. Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, Yamanaka M: Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol. 1997 Jul;121(6):1136-40. Pubmed
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. Pubmed
  3. Miyashita Y, Furukawa T, Kamegaya E, Yoshii M, Nukada T: A region of N-type Ca(2+) channel critical for blockade by the dihydropyridine amlodipine. Eur J Pharmacol. 2010 Apr 25;632(1-3):14-22. Epub 2010 Jan 22. Pubmed
  4. Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, Esashi A, Taniguchi R, Yanagisawa T, Tan-no K, Tadano T, Kitamura K, Kisara K: Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. Eur J Pharmacol. 2001 May 11;419(2-3):175-81. Pubmed
  5. Ogihara T, Kano T, Kakinuma C: Evaluation of the inhibitory effect of dihydropyridines on N-type calcium channel by virtual three-dimensional pharmacophore modeling. Arzneimittelforschung. 2009;59(6):283-8. Pubmed
  6. Qu YL, Sugiyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Comparison of binding affinities of omega-conotoxin and amlodipine to N-type Ca2+ channels in rat brain. Zhongguo Yao Li Xue Bao. 1998 Mar;19(2):97-100. Pubmed

7. Voltage-dependent calcium channel subunit alpha-2/delta-3

Pharmacological action: unknown
Actions: inhibitor

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G) (By similarity)

Organism class: human
UniProt ID: Q8IZS8 Link_out
Gene: CACNA2D3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, Yamanaka M: Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol. 1997 Jul;121(6):1136-40. Pubmed
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. Pubmed
  3. Miyashita Y, Furukawa T, Kamegaya E, Yoshii M, Nukada T: A region of N-type Ca(2+) channel critical for blockade by the dihydropyridine amlodipine. Eur J Pharmacol. 2010 Apr 25;632(1-3):14-22. Epub 2010 Jan 22. Pubmed
  4. Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, Esashi A, Taniguchi R, Yanagisawa T, Tan-no K, Tadano T, Kitamura K, Kisara K: Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. Eur J Pharmacol. 2001 May 11;419(2-3):175-81. Pubmed
  5. Ogihara T, Kano T, Kakinuma C: Evaluation of the inhibitory effect of dihydropyridines on N-type calcium channel by virtual three-dimensional pharmacophore modeling. Arzneimittelforschung. 2009;59(6):283-8. Pubmed
  6. Qu YL, Sugiyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Comparison of binding affinities of omega-conotoxin and amlodipine to N-type Ca2+ channels in rat brain. Zhongguo Yao Li Xue Bao. 1998 Mar;19(2):97-100. Pubmed

8. Voltage-gated calcium channel beta 1 subunit splice variant CavB1d

Pharmacological action: unknown
Actions: inhibitor
Organism class: human
UniProt ID: Q6TME4 Link_out
Gene: CACNB1 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, Yamanaka M: Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol. 1997 Jul;121(6):1136-40. Pubmed
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. Pubmed
  3. Miyashita Y, Furukawa T, Kamegaya E, Yoshii M, Nukada T: A region of N-type Ca(2+) channel critical for blockade by the dihydropyridine amlodipine. Eur J Pharmacol. 2010 Apr 25;632(1-3):14-22. Epub 2010 Jan 22. Pubmed
  4. Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, Esashi A, Taniguchi R, Yanagisawa T, Tan-no K, Tadano T, Kitamura K, Kisara K: Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. Eur J Pharmacol. 2001 May 11;419(2-3):175-81. Pubmed
  5. Ogihara T, Kano T, Kakinuma C: Evaluation of the inhibitory effect of dihydropyridines on N-type calcium channel by virtual three-dimensional pharmacophore modeling. Arzneimittelforschung. 2009;59(6):283-8. Pubmed
  6. Qu YL, Sugiyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Comparison of binding affinities of omega-conotoxin and amlodipine to N-type Ca2+ channels in rat brain. Zhongguo Yao Li Xue Bao. 1998 Mar;19(2):97-100. Pubmed

9. Carbonic anhydrase 1

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00915 Link_out
Gene: CA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Puscas I, Gilau L, Coltau M, Pasca R, Domuta G, Baican M, Hecht A: Hypotensive effect of calcium channel blockers is parallel with carbonic anhydrase I inhibition. Clin Pharmacol Ther. 2000 Oct;68(4):443-9. Pubmed
  2. Puscas L, Gilau L, Coltau M, Pasca R, Domuta G, Baican M, Hecht A: Calcium channel blockers reduce blood pressure in part by inhibiting vascular smooth muscle carbonic anhydrase I. Cardiovasc Drugs Ther. 2000 Oct;14(5):523-8. Pubmed
  3. Puscas I, Coltau M, Baican M, Pasca R, Domuta G, Hecht A: Vasoconstrictive drugs increase carbonic anhydrase I in vascular smooth muscle while vasodilating drugs reduce the activity of this isozyme by a direct mechanism of action. Drugs Exp Clin Res. 2001;27(2):53-60. 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. Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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

2. Cytochrome P450 3A5

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: 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.

3. Cytochrome P450 3A7

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: 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.

4. Cytochrome P450 1A2

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. 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. Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. 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

5. Cytochrome P450 1A1

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: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. 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 2B6

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

References:
  1. Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. 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 2A6

Actions: inhibitor

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
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 2C8

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. 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

9. Cytochrome P450 2C9

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. 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

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: 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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19