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Identification
Name Nimodipine
Accession Number DB00393 (APRD00612)
Type small molecule
Groups approved
Description

Nimodipine is a 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, nimodipine prevents calcium-dependent smooth muscle contraction and subsequent vasoconstriction. Compared to other calcium channel blocking agents, nimodipine exhibits greater effects on cerebral circulation than on peripheral circulation. Nimodipine is used to as an adjunct to improve the neurologic outcome following subarachnoid hemorrhage from ruptured intracranial aneurysm.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Nimodipino [INN-Spanish]
Nimodipinum [INN-Latin]
Salts Not Available
Brand names
Name Company
Nimotop Bayer
Periplum
Brand mixtures Not Available
Categories
  • Antihypertensive Agents
  • Vasodilator Agents
  • Calcium Channel Blockers
CAS number 66085-59-4
Weight Average: 418.4403
Monoisotopic: 418.174001196
Chemical Formula C21H26N2O7
InChI Key InChIKey=UIAGMCDKSXEBJQ-UHFFFAOYSA-N
InChI
InChI=1S/C21H26N2O7/c1-12(2)30-21(25)18-14(4)22-13(3)17(20(24)29-10-9-28-5)19(18)15-7-6-8-16(11-15)23(26)27/h6-8,11-12,19,22H,9-10H2,1-5H3
Plain Text
IUPAC Name
3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
COCCOC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)C
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
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
Pharmacology
Indication For use as an adjunct to improve neurologic outcome following subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms by reducing the incidence and severity of ischemic deficits.
Pharmacodynamics Nimodipine belongs to the class of pharmacological agents known as calcium channel blockers. Nimodipine is indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured congenital aneurysms who are in good neurological condition post-ictus (e.g., Hunt and Hess Grades I-III). The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly lipophilic, allowing it to cross the blood brain barrier.
Mechanism of action Although the precise mechanism of action is not known, nimodipine blocks intracellular influx of calcium through voltage-dependent and receptor-operated slow calcium channels across the membranes of myocardial, vascular smooth muscle, and neuronal cells. Nimodipine binds specifically to L-type voltage-gated calcium channels. The inhibition of calcium ion transfer results in the inhibition of vascular smooth muscle contraction. Evidence suggests that the dilation of small cerebral resistance vessels, with a resultant increase in collateral circulation, and/or a direct effect involving the prevention of calcium overload in neurons may be responsible for nimodipine's clinical effect in patients with subarachnoid hemorrhage.
Absorption Bioavailability is 100% following intravenous administration and 3-30% following oral administration due to extensive first-pass metabolism.
Volume of distribution Not Available
Protein binding 95%
Metabolism Hepatic metabolism via cytochrome P450 3A4.
Route of elimination Not Available
Half life 1.7-9 hours
Clearance Not Available
Toxicity Symptoms of overdosage would be expected to be related to cardiovascular effects such as excessive peripheral vasodilation with marked systemic hypotension.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00380 Nimodipine Pathway SMP00380
Pharmacoeconomics
Manufacturers
  • Banner pharmacaps inc
  • Barr laboratories inc
  • Sun pharmaceutical industries inc
  • Bayer pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Capsule Oral 30 mg
Tablet, film coated Oral 30 mg
Prices
Unit description Cost Unit
NiMODipine 100 30 mg capsule Box 952.07 USD box
Nimotop 30 mg capsule 9.87 USD capsule
Nimodipine 30 mg capsule 9.69 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 125 °C Not Available
logP 3.05 MASUMOTO,K ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 1.20e-02 g/l ALOGPS
logP 3.41 ALOGPS
logP 2.54 ChemAxon
logS -4.5 ALOGPS
pKa (strongest basic) 5.41 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 119.68 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 112.38 ChemAxon
polarizability 43.17 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Janjua N, Mayer SA: Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care. 2003 Apr;9(2):113-9. Pubmed
  2. Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Boone SC, Chou SN, Kelly DL, Weir BK, Crabbe RA, Lavik PJ, Rosenbloom SB, Dorsey FC, Ingram CR, Mellits DE, Bertsch LA, Boisvert DP, Hundley MB, Johnson RK, Strom JA, Transou CR: Cerebral arterial spasm—a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med. 1983 Mar 17;308(11):619-24. Pubmed
  3. Belfort MA, Anthony J, Saade GR, Allen JC Jr: A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med. 2003 Jan 23;348(4):304-11. Pubmed#
    Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  4. Tomassoni D, Lanari A, Silvestrelli G, Traini E, Amenta F: Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies. Clin Exp Hypertens. 2008 Nov;30(8):744-66. Pubmed
  5. Vergouwen MD, Vermeulen M, Roos YB: Effect of nimodipine on outcome in patients with traumatic subarachnoid haemorrhage: a systematic review. Lancet Neurol. 2006 Dec;5(12):1029-32. Pubmed
External Links
Resource Link
KEGG Drug D00438 Link_out
KEGG Compound C07267 Link_out
PubChem Compound 4497 Link_out
PubChem Substance 46508497 Link_out
ChemSpider 4341 Link_out
BindingDB 50011690 Link_out
Therapeutic Targets Database DAP000306 Link_out
PharmGKB PA450633 Link_out
IUPHAR 2523 Link_out
Guide to Pharmacology 2523 Link_out
Drug Product Database 2155923 Link_out
RxList http://www.rxlist.com/cgi/generic2/nimodip.htm Link_out
Drugs.com http://www.drugs.com/cdi/nimodipine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Nimodipine Link_out
ATC Codes
  • C08CA06
AHFS Codes
  • 24:28.08
PDB Entries Not Available
FDA label show (504 KB)
MSDS show (73.3 KB)
Interactions
Drug Interactions
Drug Interaction
Cimetidine Cimetidine increases the effect of the calcium channel blocker, nimodipine.
Quinupristin This combination presents an increased risk of toxicity
Telithromycin Telithromycin may reduce clearance of Nimodipine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Nimodipine if Telithromycin is initiated, discontinued or dose changed.
Thiopental The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nimodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nimodipine if Thiopental is initiated, discontinued or dose changed.
Tipranavir Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Nimodipine. Monitor for changes in Nimodipine therapeutic and adverse effects if Tipranavir is initiated, discontinued or dose changed.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Valproic Acid Valproic acid increases the effect of nimodipine
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of nimodipine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nimodipine if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Grapefruit down regulates post-translational expression of CYP3A4, the major metabolizing enzyme of nimodipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of nimodipine and may cause toxicity. Avoid grapefruit products while on this medication.
  • Take at the same time each day, with or without food, but always in the same manner.
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. Marchetti C, Usai C: High affinity block by nimodipine of the internal calcium elevation in chronically depolarized rat cerebellar granule neurons. Neurosci Lett. 1996 Mar 29;207(2):77-80. Pubmed
  3. 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. Weant KA, Ramsey CN 3rd, Cook AM: Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage. Pharmacotherapy. 2010 Apr;30(4):405-17. Pubmed
  5. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine Enhancement of {alpha}2 Adrenergic Modulation of NMDA Receptor via a Mechanism Independent of Ca2+ Channel Blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. Epub 2010 Mar 24. Pubmed
  6. Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  7. Kumar R, Mehra R, Ray SB: L-type calcium channel blockers, morphine and pain: Newer insights. Indian J Anaesth. 2010 Mar;54(2):127-31. Pubmed
  8. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. 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. 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
  2. Weant KA, Ramsey CN 3rd, Cook AM: Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage. Pharmacotherapy. 2010 Apr;30(4):405-17. Pubmed
  3. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine Enhancement of {alpha}2 Adrenergic Modulation of NMDA Receptor via a Mechanism Independent of Ca2+ Channel Blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. Epub 2010 Mar 24. Pubmed
  4. Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  5. Kumar R, Mehra R, Ray SB: L-type calcium channel blockers, morphine and pain: Newer insights. Indian J Anaesth. 2010 Mar;54(2):127-31. Pubmed
  6. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. 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. Weant KA, Ramsey CN 3rd, Cook AM: Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage. Pharmacotherapy. 2010 Apr;30(4):405-17. Pubmed
  2. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine Enhancement of {alpha}2 Adrenergic Modulation of NMDA Receptor via a Mechanism Independent of Ca2+ Channel Blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. Epub 2010 Mar 24. Pubmed
  3. Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  4. Kumar R, Mehra R, Ray SB: L-type calcium channel blockers, morphine and pain: Newer insights. Indian J Anaesth. 2010 Mar;54(2):127-31. 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. 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
  2. Weant KA, Ramsey CN 3rd, Cook AM: Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage. Pharmacotherapy. 2010 Apr;30(4):405-17. Pubmed
  3. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine Enhancement of {alpha}2 Adrenergic Modulation of NMDA Receptor via a Mechanism Independent of Ca2+ Channel Blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. Epub 2010 Mar 24. Pubmed
  4. Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  5. Kumar R, Mehra R, Ray SB: L-type calcium channel blockers, morphine and pain: Newer insights. Indian J Anaesth. 2010 Mar;54(2):127-31. Pubmed
  6. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. 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. Weant KA, Ramsey CN 3rd, Cook AM: Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage. Pharmacotherapy. 2010 Apr;30(4):405-17. Pubmed
  2. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine Enhancement of {alpha}2 Adrenergic Modulation of NMDA Receptor via a Mechanism Independent of Ca2+ Channel Blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. Epub 2010 Mar 24. Pubmed
  3. Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  4. Kumar R, Mehra R, Ray SB: L-type calcium channel blockers, morphine and pain: Newer insights. Indian J Anaesth. 2010 Mar;54(2):127-31. Pubmed
  5. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. 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. 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. Weant KA, Ramsey CN 3rd, Cook AM: Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage. Pharmacotherapy. 2010 Apr;30(4):405-17. Pubmed
  4. Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  5. Kumar R, Mehra R, Ray SB: L-type calcium channel blockers, morphine and pain: Newer insights. Indian J Anaesth. 2010 Mar;54(2):127-31. Pubmed
  6. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. 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. Weant KA, Ramsey CN 3rd, Cook AM: Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage. Pharmacotherapy. 2010 Apr;30(4):405-17. Pubmed
  2. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine Enhancement of {alpha}2 Adrenergic Modulation of NMDA Receptor via a Mechanism Independent of Ca2+ Channel Blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. Epub 2010 Mar 24. Pubmed
  3. Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  4. Kumar R, Mehra R, Ray SB: L-type calcium channel blockers, morphine and pain: Newer insights. Indian J Anaesth. 2010 Mar;54(2):127-31. Pubmed
  5. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. 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. Weant KA, Ramsey CN 3rd, Cook AM: Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage. Pharmacotherapy. 2010 Apr;30(4):405-17. Pubmed
  2. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine Enhancement of {alpha}2 Adrenergic Modulation of NMDA Receptor via a Mechanism Independent of Ca2+ Channel Blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. Epub 2010 Mar 24. Pubmed
  3. Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  4. Kumar R, Mehra R, Ray SB: L-type calcium channel blockers, morphine and pain: Newer insights. Indian J Anaesth. 2010 Mar;54(2):127-31. Pubmed
  5. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. Pubmed

9. Mineralocorticoid receptor

Pharmacological action: unknown
Actions: antagonist

Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels

Organism class: human
UniProt ID: P08235 Link_out
Gene: NR3C2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dietz JD, Du S, Bolten CW, Payne MA, Xia C, Blinn JR, Funder JW, Hu X: A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension. 2008 Mar;51(3):742-8. Epub 2008 Feb 4. Pubmed

10. Aryl hydrocarbon receptor

Pharmacological action: unknown
Actions: agonist

Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues

Organism class: human
UniProt ID: P35869 Link_out
Gene: AHR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hu W, Sorrentino C, Denison MS, Kolaja K, Fielden MR: Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro. Mol Pharmacol. 2007 Jun;71(6):1475-86. Epub 2007 Feb 27. Pubmed
Enzymes

1. Cytochrome P450 3A4

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