Identification

Name
Nimodipine
Accession Number
DB00393  (APRD00612)
Type
Small Molecule
Groups
Approved, Investigational
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
Synonyms
  • 2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-β-methoxyethyl ester 5-isopropyl ester
  • isopropyl 2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate
  • isopropyl 2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate
  • Nimodipino
  • Nimodipinum
External IDs
BAY E 9736 / BAY-E-9736
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NimotopTablet30 mgOralBayer2009-07-24Not applicableCanada
NimotopCapsule, gelatin coated30 mg/1OralBayer1988-12-282009-04-30Us
Nimotop - Cap 30mgCapsule30 mgOralBayer1989-12-312009-08-06Canada
Nimotop Cap 30mgCapsule30 mgOralMiles Inc. Pharmaceutical Division1989-12-311996-10-02Canada
Nimotop I.V.-0.2mg/mlLiquid.2 mgIntravenousBayer1996-10-082000-09-19Canada
Nimotop IV 0.2mg/mlLiquid0.2 mgIntravenousMiles Inc. Pharmaceutical Division1992-12-312000-08-01Canada
NymalizeSolution30 mg/10mLOralArbor Pharmaceuticals2017-04-06Not applicableUs
NymalizeSolution60 mg/20mLOralArbor Pharmaceuticals2013-06-03Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NimodipineCapsule, liquid filled30 mg/1OralAscend Laboratories, LLC2015-01-01Not applicableUs
NimodipineCapsule30 mg/1OralCaraco Pharmaceutical Laboratories, Ltd.2007-06-28Not applicableUs
NimodipineCapsule, liquid filled30 mg/1OralAmerincan Health Packaging2015-02-17Not applicableUs
NimodipineCapsule, liquid filled30 mg/1OralMc Kesson2015-01-01Not applicableUs
NimodipineCapsule, liquid filled30 mg/1OralHeritage2017-11-07Not applicableUs
NimodipineCapsule, liquid filled30 mg/1OralHeritage2008-03-21Not applicableUs
NimodipineCapsule, liquid filled30 mg/1OralGolden State Medical Supply2008-03-212018-01-01Us
NimodipineCapsule30 mg/1OralCardinal Health2007-06-282013-07-31Us
NimodipineCapsule30 mg/1OralANI Pharmaceuticals, Inc.2015-11-01Not applicableUs
NimodipineCapsule, liquid filled30 mg/1OralBarr Laboratories2007-05-252014-06-30Us0555 098020180907 15195 1rndj61
International/Other Brands
Periplum
Categories
UNII
57WA9QZ5WH
CAS number
66085-59-4
Weight
Average: 418.4403
Monoisotopic: 418.174001196
Chemical Formula
C21H26N2O7
InChI Key
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
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

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.

Associated Conditions
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.

TargetActionsOrganism
AVoltage-dependent L-type calcium channel subunit alpha-1C
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit alpha-1D
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit alpha-1F
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit alpha-1S
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit beta-1
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit beta-2
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit beta-3
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit beta-4
inhibitor
Human
UMineralocorticoid receptor
antagonist
Human
UAryl hydrocarbon receptor
agonist
Human
Absorption

In humans, nimodipine is rapidly absorbed after oral administration, and peak concentrations are generally attained within one hour. 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% bound to plasma protein

Metabolism

Hepatic metabolism via CYP 3A4.

Route of elimination

Nimodipine is eliminated almost exclusively in the form of metabolites and less than 1% is recovered in the urine as unchanged drug. Numerous metabolites, all of which are either inactive or considerably less active than the parent compound, have been identified.

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
PathwayCategory
Nimodipine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbafunginThe therapeutic efficacy of Abafungin can be increased when used in combination with Nimodipine.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Nimodipine.
AcalabrutinibThe serum concentration of Nimodipine can be increased when it is combined with Acalabrutinib.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Nimodipine.
AceclofenacThe therapeutic efficacy of Nimodipine can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Nimodipine can be decreased when used in combination with Acemetacin.
AcepromazineThe risk or severity of hypotension can be increased when Acepromazine is combined with Nimodipine.
Acetylsalicylic acidThe therapeutic efficacy of Nimodipine can be decreased when used in combination with Acetylsalicylic acid.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Nimodipine.
AlbaconazoleThe therapeutic efficacy of Albaconazole can be increased when used in combination with Nimodipine.
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.

References

General References
  1. Janjua N, Mayer SA: Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care. 2003 Apr;9(2):113-9. [PubMed:12657973]
  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:6338383]
  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:12540643]
  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. doi: 10.3340/jkns.2009.46.3.239. Epub 2009 Sep 30. [PubMed:19844625]
  5. 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. doi: 10.1080/10641960802580232. [PubMed:19021025]
  6. 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:17110283]
External Links
Human Metabolome Database
HMDB0014537
KEGG Drug
D00438
KEGG Compound
C07267
PubChem Compound
4497
PubChem Substance
46508497
ChemSpider
4341
BindingDB
50011690
ChEBI
7575
ChEMBL
CHEMBL1428
Therapeutic Targets Database
DAP000306
PharmGKB
PA450633
IUPHAR
2523
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nimodipine
ATC Codes
C08CA06 — Nimodipine
AHFS Codes
  • 24:28.08 — Dihydropyridines
FDA label
Download (504 KB)
MSDS
Download (73.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingOtherSchizo Affective Disorder / Schizophrenic Disorders1
1CompletedNot AvailableProgranulin Mutation Carriers1
1CompletedTreatmentAIDS-Related Dementia Complex / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentCocaine-Related Disorders1
1, 2CompletedTreatmentRuptured Berry Aneurysm / Ruptured Cerebral Aneurysm1
2CompletedTreatmentCocaine-Related Disorders1
2TerminatedTreatmentInfertilities1
2WithdrawnTreatmentCerebrovascular Accident, Acute / Vasospasm1
4CompletedTreatmentCerebral Infarctions1
4CompletedTreatmentDementias1
4RecruitingTreatmentReversible cerebral vasoconstriction syndrome1
4TerminatedTreatmentDepression1
4Unknown StatusPreventionMild Cognitive Impairment (MCI) / Strokes1
Not AvailableActive Not RecruitingNot AvailableSubarachnoid Hemorrhage, Aneurysmal1
Not AvailableCompletedPreventionProphylaxis of preeclampsia1
Not AvailableCompletedTreatmentAnovulatory cycle / Polycystic Ovarian Syndrome / Unexplained Infertility1
Not AvailableTerminatedTreatmentMild Cognitive Impairment (MCI)1

Pharmacoeconomics

Manufacturers
  • Banner pharmacaps inc
  • Barr laboratories inc
  • Sun pharmaceutical industries inc
  • Bayer pharmaceuticals corp
Packagers
  • Amerisource Health Services Corp.
  • Banner Pharmacaps Inc.
  • Barr Pharmaceuticals
  • Bayer Healthcare
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Catalent Pharma Solutions
  • Heritage Pharmaceuticals
  • Neuman Distributors Inc.
  • Pharmaceutics International Inc.
  • Sandhills Packaging Inc.
Dosage forms
FormRouteStrength
CapsuleOral30 mg/1
Capsule, liquid filledOral30 mg/1
Capsule, gelatin coatedOral30 mg/1
TabletOral30 mg
CapsuleOral30 mg
LiquidIntravenous.2 mg
LiquidIntravenous0.2 mg
SolutionOral30 mg/10mL
SolutionOral60 mg/20mL
Prices
Unit descriptionCostUnit
NiMODipine 100 30 mg capsule Box952.07USD box
Nimotop 30 mg capsule9.87USD capsule
Nimodipine 30 mg capsule9.69USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)125 °CNot Available
logP3.05MASUMOTO,K ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.012 mg/mLALOGPS
logP3.41ALOGPS
logP2.54ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)5.41ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area119.68 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity112.38 m3·mol-1ChemAxon
Polarizability43.17 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9387
Blood Brain Barrier-0.9358
Caco-2 permeable-0.5838
P-glycoprotein substrateSubstrate0.752
P-glycoprotein inhibitor IInhibitor0.9287
P-glycoprotein inhibitor IIInhibitor0.9098
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.8151
CYP450 2D6 substrateNon-substrate0.9118
CYP450 3A4 substrateSubstrate0.7571
CYP450 1A2 substrateInhibitor0.9108
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.8248
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8557
Ames testNon AMES toxic0.5976
CarcinogenicityNon-carcinogens0.6953
BiodegradationNot ready biodegradable0.8797
Rat acute toxicity2.5326 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6468
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-0149000000-2a019013c0386ca13362

Taxonomy

Description
This compound belongs to the class of organic compounds known as dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Hydropyridines
Direct Parent
Dihydropyridinecarboxylic acids and derivatives
Alternative Parents
Nitrobenzenes / Nitroaromatic compounds / Dicarboxylic acids and derivatives / Vinylogous amides / Enoate esters / Amino acids and derivatives / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Dialkyl ethers / Dialkylamines
show 7 more
Substituents
Dihydropyridinecarboxylic acid derivative / Nitrobenzene / Nitroaromatic compound / Monocyclic benzene moiety / Dicarboxylic acid or derivatives / Benzenoid / Vinylogous amide / Enoate ester / Alpha,beta-unsaturated carboxylic ester / Amino acid or derivatives
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
C-nitro compound, diester, dihydropyridine (CHEBI:7575)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
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, hor...
Gene Name
CACNA1C
Uniprot ID
Q13936
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1C
Molecular Weight
248974.1 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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:8731425]
  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. doi: 10.1592/phco.30.4.405. [PubMed:20334460]
  4. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine enhancement of alpha2 adrenergic modulation of NMDA receptor via a mechanism independent of Ca2+ channel blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. doi: 10.1167/iovs.09-4613. Epub 2010 Mar 24. [PubMed:20335610]
  5. 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. doi: 10.3340/jkns.2009.46.3.239. Epub 2009 Sep 30. [PubMed:19844625]
  6. 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. doi: 10.4103/0019-5049.63652. [PubMed:20661350]
  7. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. [PubMed:17705883]
  8. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity involved sa node cell action potential
Specific Function
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, hor...
Gene Name
CACNA1D
Uniprot ID
Q01668
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1D
Molecular Weight
245138.75 Da
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. doi: 10.1124/mol.108.049981. Epub 2008 Nov 24. [PubMed:19029287]
  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. doi: 10.1592/phco.30.4.405. [PubMed:20334460]
  3. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine enhancement of alpha2 adrenergic modulation of NMDA receptor via a mechanism independent of Ca2+ channel blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. doi: 10.1167/iovs.09-4613. Epub 2010 Mar 24. [PubMed:20335610]
  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. doi: 10.3340/jkns.2009.46.3.239. Epub 2009 Sep 30. [PubMed:19844625]
  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. doi: 10.4103/0019-5049.63652. [PubMed:20661350]
  6. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. [PubMed:17705883]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
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, hor...
Gene Name
CACNA1F
Uniprot ID
O60840
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1F
Molecular Weight
220675.9 Da
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. doi: 10.1592/phco.30.4.405. [PubMed:20334460]
  2. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine enhancement of alpha2 adrenergic modulation of NMDA receptor via a mechanism independent of Ca2+ channel blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. doi: 10.1167/iovs.09-4613. Epub 2010 Mar 24. [PubMed:20335610]
  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. doi: 10.3340/jkns.2009.46.3.239. Epub 2009 Sep 30. [PubMed:19844625]
  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. doi: 10.4103/0019-5049.63652. [PubMed:20661350]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
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, hor...
Gene Name
CACNA1S
Uniprot ID
Q13698
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1S
Molecular Weight
212348.1 Da
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:16675661]
  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. doi: 10.1592/phco.30.4.405. [PubMed:20334460]
  3. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine enhancement of alpha2 adrenergic modulation of NMDA receptor via a mechanism independent of Ca2+ channel blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. doi: 10.1167/iovs.09-4613. Epub 2010 Mar 24. [PubMed:20335610]
  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. doi: 10.3340/jkns.2009.46.3.239. Epub 2009 Sep 30. [PubMed:19844625]
  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. doi: 10.4103/0019-5049.63652. [PubMed:20661350]
  6. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. [PubMed:17705883]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
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 ina...
Gene Name
CACNB1
Uniprot ID
Q02641
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-1
Molecular Weight
65712.995 Da
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. doi: 10.1592/phco.30.4.405. [PubMed:20334460]
  2. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine enhancement of alpha2 adrenergic modulation of NMDA receptor via a mechanism independent of Ca2+ channel blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. doi: 10.1167/iovs.09-4613. Epub 2010 Mar 24. [PubMed:20335610]
  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. doi: 10.3340/jkns.2009.46.3.239. Epub 2009 Sep 30. [PubMed:19844625]
  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. doi: 10.4103/0019-5049.63652. [PubMed:20661350]
  5. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. [PubMed:17705883]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
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 ina...
Gene Name
CACNB2
Uniprot ID
Q08289
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-2
Molecular Weight
73579.925 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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. doi: 10.1592/phco.30.4.405. [PubMed:20334460]
  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. doi: 10.3340/jkns.2009.46.3.239. Epub 2009 Sep 30. [PubMed:19844625]
  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. doi: 10.4103/0019-5049.63652. [PubMed:20661350]
  5. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. [PubMed:17705883]
  6. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
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 ina...
Gene Name
CACNB3
Uniprot ID
P54284
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-3
Molecular Weight
54531.425 Da
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. doi: 10.1592/phco.30.4.405. [PubMed:20334460]
  2. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine enhancement of alpha2 adrenergic modulation of NMDA receptor via a mechanism independent of Ca2+ channel blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. doi: 10.1167/iovs.09-4613. Epub 2010 Mar 24. [PubMed:20335610]
  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. doi: 10.3340/jkns.2009.46.3.239. Epub 2009 Sep 30. [PubMed:19844625]
  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. doi: 10.4103/0019-5049.63652. [PubMed:20661350]
  5. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. [PubMed:17705883]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
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 ina...
Gene Name
CACNB4
Uniprot ID
O00305
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-4
Molecular Weight
58168.625 Da
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. doi: 10.1592/phco.30.4.405. [PubMed:20334460]
  2. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA: Nimodipine enhancement of alpha2 adrenergic modulation of NMDA receptor via a mechanism independent of Ca2+ channel blocking. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4174-80. doi: 10.1167/iovs.09-4613. Epub 2010 Mar 24. [PubMed:20335610]
  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. doi: 10.3340/jkns.2009.46.3.239. Epub 2009 Sep 30. [PubMed:19844625]
  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. doi: 10.4103/0019-5049.63652. [PubMed:20661350]
  5. Keyrouz SG, Diringer MN: Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. [PubMed:17705883]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates targ...
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107066.575 Da
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. doi: 10.1161/HYPERTENSIONAHA.107.103580. Epub 2008 Feb 4. [PubMed:18250364]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Transcription regulatory region dna binding
Specific Function
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...
Gene Name
AHR
Uniprot ID
P35869
Uniprot Name
Aryl hydrocarbon receptor
Molecular Weight
96146.705 Da
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:17327465]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Liu XQ, Ren YL, Qian ZY, Wang GJ: Enzyme kinetics and inhibition of nimodipine metabolism in human liver microsomes. Acta Pharmacol Sin. 2000 Aug;21(8):690-4. [PubMed:11501176]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Liu XQ, Ren YL, Qian ZY, Wang GJ: Enzyme kinetics and inhibition of nimodipine metabolism in human liver microsomes. Acta Pharmacol Sin. 2000 Aug;21(8):690-4. [PubMed:11501176]

Drug created on June 13, 2005 07:24 / Updated on September 23, 2018 19:37