U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C21H26N2O7
Molecular Weight 418.4412
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NIMODIPINE

SMILES

CC(C)OC(=O)C1=C(C)NC(=C(C1c2cccc(c2)N(=O)=O)C(=O)OCCOC)C

InChI

InChIKey=UIAGMCDKSXEBJQ-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C21H26N2O7
Molecular Weight 418.4412
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/2565839

Nimodipine is a dihydropyridine calcium antagonist which has been shown to dilate cerebral arterioles and increase cerebral blood flow in animals and humans. It has potential in the treatment of a range of cerebrovascular disorders. Major interest to date, however, has focused on its use in the prevention and treatment of the delayed ischaemic neurological deficits that frequently occur in patients with subarachnoid haemorrhages as a result of sustained cerebral vasospasm. Nimodipine, a Ca2+ antagonist with cerebrovasodilatory and anti-ischemic effects, binds to rat, guinea pig, and human brain membranes with high affinity (less than 1 nM). Only at higher concentrations has nimodipine been reported to block the release of some neurotransmitters and hormones from neuronal tissue.

CNS Activity

Curator's Comment:: Nimodipine has adequate brain penetration, dilates intracranial vessels in animals and humans. Experimental data suggest direct neuronal action of nimodipine in animals. https://www.ncbi.nlm.nih.gov/pubmed/2565839

Originator

Curator's Comment:: # Meyer et al, patented to Bayer AG

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.27 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NIMOTOP

Approved Use

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 intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V).

Launch Date

5.9927042E11
Primary
NYMALIZE

Approved Use

NYMALIZE is a dihydropyridine calcium channel blocker indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V).

Launch Date

1.36805758E12
Primary
NIMODIPINE

Approved Use

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 intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V).

Launch Date

1.17797762E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
20 nM
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIMODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
29 ng/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIMODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
100 nM × h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIMODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
47.6 ng × h/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIMODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.2 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIMODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
2.27 h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIMODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
NIMODIPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
60 mg 6 times / day multiple, oral
Recommended
Dose: 60 mg, 6 times / day
Route: oral
Route: multiple
Dose: 60 mg, 6 times / day
Sources:
unhealthy, 47 (21-63)
n = 38
Health Status: unhealthy
Condition: subarachnoid haemorrhage
Age Group: 47 (21-63)
Sex: M+F
Population Size: 38
Sources:
Other AEs: Death...
Other AEs:
Death (grade 5, 4 patients)
Sources:
120 mg 6 times / day multiple, oral
Highest studied dose
Dose: 120 mg, 6 times / day
Route: oral
Route: multiple
Dose: 120 mg, 6 times / day
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Condition: subarachnoid haemorrhage
Age Group: adult
Sex: unknown
Population Size: 4
Sources:
Other AEs: Blood pressure decreased...
2 mg/h 1 times / day multiple, intravenous
Recommended
Dose: 2 mg/h, 1 times / day
Route: intravenous
Route: multiple
Dose: 2 mg/h, 1 times / day
Sources:
unhealthy, adult
n = 120
Health Status: unhealthy
Condition: subarachnoid hemorrhage
Age Group: adult
Sex: M+F
Population Size: 120
Sources:
Other AEs: Death...
Other AEs:
Death (grade 5, 7 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Death grade 5, 4 patients
60 mg 6 times / day multiple, oral
Recommended
Dose: 60 mg, 6 times / day
Route: oral
Route: multiple
Dose: 60 mg, 6 times / day
Sources:
unhealthy, 47 (21-63)
n = 38
Health Status: unhealthy
Condition: subarachnoid haemorrhage
Age Group: 47 (21-63)
Sex: M+F
Population Size: 38
Sources:
Blood pressure decreased 50%
120 mg 6 times / day multiple, oral
Highest studied dose
Dose: 120 mg, 6 times / day
Route: oral
Route: multiple
Dose: 120 mg, 6 times / day
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Condition: subarachnoid haemorrhage
Age Group: adult
Sex: unknown
Population Size: 4
Sources:
Death grade 5, 7 patients
2 mg/h 1 times / day multiple, intravenous
Recommended
Dose: 2 mg/h, 1 times / day
Route: intravenous
Route: multiple
Dose: 2 mg/h, 1 times / day
Sources:
unhealthy, adult
n = 120
Health Status: unhealthy
Condition: subarachnoid hemorrhage
Age Group: adult
Sex: M+F
Population Size: 120
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
Drug as victim

Drug as victim

Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Effect of nimodipine (Bay e 9736) on postischaemic cerebrovascular reactivity, as revealed by measuring regional cerebral blood flow (rCBF).
1982
Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage.
1983 Mar 17
Cerebral blood flow and neurologic outcome when nimodipine is given after complete cerebral ischemia in the dog.
1984 Mar
Magnetic resonance imaging in the evaluation of nimodipine-treated acute experimental focal cerebral ischemia.
1986
[Ergotism with cerebral complications. Case report and review of the literature].
1986 Apr 5
[Nimodipine, nifedipine and vincamine improve amnesia induced by anisodine and sodium nitrite in rats and mice].
1986 Oct
Non-vascular action of calcium blockers in migraine: pupillopharmacological study.
1986 Oct-Dec
Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications.
1987 Nov
Ca2+ modulators as antidotes to imipramine and neurotransmitter toxicity.
1987 Sep
Nimodipine treatment of subarachnoid hemorrhage.
1988
Therapeutic trial of intravenous nimodipine in patients with established cerebral vasospasm after rupture of intracranial aneurysms.
1988 Aug
Effects of nimodipine on the production of thromboxane A2 following total global cerebral ischemia.
1988 Sep
Calcium channel inhibitors prevent apomorphine- and oxytocin-induced penile erection and yawning in male rats.
1989 Aug 3
Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial.
1989 Mar 11
Effect of treatment with nimodipine in patients with mild and moderate essential hypertension.
1990 Apr
HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists.
1990 Apr 20
Oxytocin-induced penile erection and yawning: role of calcium and prostaglandins.
1990 Mar
Nimodipine pretreatment improves cerebral blood flow and reduces brain edema in conscious rats subjected to focal cerebral ischemia.
1990 Nov
Protective effect of nimodipine against ischemic neuronal damage in rat hippocampus without changing postischemic cerebral blood flow.
1990 Sep
Quinine-induced tinnitus in rats.
1991 Oct
Effects of the combination of ketoconazole and calcium channel antagonists against Candida albicans in vitro.
1993 Jul
Sinus arrest after nimodipine treatment for a head injury.
1994
Cocaine toxicity and the calcium channel blockers nifedipine and nimodipine in rats.
1994 Jan-Feb
Hypotensive effect of nimodipine during treatment for aneurysmal subarachnoid haemorrhage.
1995
Preliminary study on controlled hypotension induced by nimodipine in craniocerebral surgery.
1995 Jun
Effect of calcium channel blockers on withdrawal syndrome of lorazepam in rats.
1996 Jun
Haemodynamic effects of intravenous nimodipine following aneurysmal subarachnoid haemorrhage: implications for monitoring.
1997 May
Dose-finding study with nimodipine: a selective central nervous system calcium channel blocker on aminophylline induced seizure models in rats.
1998 Mar 15
Use of phenytoin and other anticonvulsant prophylaxis in patients with aneurysmal subarachnoid hemorrhage.
2005 Dec
Antioxidant effect of nimodipine in young rats after pilocarpine-induced seizures.
2005 Sep
Effect of nimodipine on outcome in patients with traumatic subarachnoid haemorrhage: a systematic review.
2006 Dec
Reversible cerebral angiopathy: efficacy of nimodipine.
2006 Dec
The L-type calcium channel blocker nimodipine mitigates cytoskeletal proteins phosphorylation in dichlorvos-induced delayed neurotoxicity in rats.
2006 May
Protective effect of adenosine reuptake inhibitors in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes.
2007
[Effect of nimodipine on mechanisms of HL-60 cell apoptosis induced by cytarabine].
2007 Feb
L-type calcium channel blockade on haloperidol-induced c-Fos expression in the striatum.
2007 Nov 9
Amphetamine-induced anxiety-related behavior in animal models.
2007 Nov-Dec
Mechanisms of potassium- and capsaicin-induced axonal calcitonin gene-related peptide release: involvement of L- and T-type calcium channels and TRPV1 but not sodium channels.
2008 Feb 6
A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity.
2008 Mar
Ammonia inhibits the C-type natriuretic peptide-dependent cyclic GMP synthesis and calcium accumulation in a rat brain endothelial cell line.
2008 May
Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies.
2008 Nov
Protective effect of L-type calcium channel blockers against haloperidol-induced orofacial dyskinesia: a behavioural, biochemical and neurochemical study.
2008 Sep
Chloride channels as drug targets.
2009 Feb
Cell death induced by zinc and cadmium is mediated by clusterin in cultured mouse seminiferous tubules.
2009 Jul
Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
2009 Sep
Organophosphorus-induced delayed neuropathy: a simple and efficient therapeutic strategy.
2010 Feb 1
Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening.
2011 Feb
Biochemical, histopathological and clinical evaluation of delayed effects caused by methamidophos isoforms and TOCP in hens: ameliorative effects using control of calcium homeostasis.
2012 Dec 8
Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease.
2012 Oct
Screening of a chemical library reveals novel PXR-activating pharmacologic compounds.
2015 Jan 5
Patents

Sample Use Guides

Nimodipine is given orally in the form of soft gelatin 30 mg capsules for subarachnoid hemorrhage. The recommended oral dose is 60 mg (two 30 mg capsules) every 4 hours for 21 consecutive days.
Route of Administration: Oral
Nimodipine (1-100 μM) conferred 65±13% neuroprotection in PC12 neuronal cultures upon exposure to oxygen-glucose deprivation (OGD) and 35±6% neuroprotection towards different trophic withdrawal-induced cell death measured by lactate dehydrogenase and caspase 3 activities. The time window of nimodipine conferred neuroprotection was detected during the first 5h but not at longer OGD exposures.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:01:52 UTC 2021
Edited
by admin
on Fri Jun 25 21:01:52 UTC 2021
Record UNII
57WA9QZ5WH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NIMODIPINE
EP   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
NIMODIPINE [VANDF]
Common Name English
NIMODIPINE [MI]
Common Name English
NIMODIPINE [EP MONOGRAPH]
Common Name English
ISOPROPYL 2-METHOXYETHYL 1,4-DIHYDRO-2,6-DIMETHYL-4-(M-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLATE
Systematic Name English
PERIPLUM
Brand Name English
NIMODIPINE [MART.]
Common Name English
NSC-758476
Code English
NIMOTOP
Common Name English
3,5-PYRIDINEDICARBOXYLIC ACID, 1,4-DIHYDRO-2,6-DIMETHYL-4-(3-NITROPHENYL)-, 3-(2-METHOXYETHYL) 5-(1-METHYLETHYL) ESTER
Systematic Name English
NIMODIPINE [WHO-DD]
Common Name English
NIMODIPINE AP
Brand Name English
ADMON
Brand Name English
NIMODIPINE [USP]
Common Name English
NIMODIPINE [ORANGE BOOK]
Common Name English
NIMODIPINE [INN]
Common Name English
NIMODIPINE [JAN]
Common Name English
NEMOTAN
Brand Name English
BAY-E-9736
Code English
NIMODIPINE [USP-RS]
Common Name English
BAY E 9736
Code English
NYMALIZE
Brand Name English
NIMODIPINE [USP MONOGRAPH]
Common Name English
NIMODIPINE [USAN]
Common Name English
(+/-)-NIMODIPINE
Common Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/15/1554
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
LIVERTOX 687
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
NDF-RT N0000175421
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
NCI_THESAURUS C333
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
NDF-RT N0000000069
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
WHO-ATC C08CA06
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
FDA ORPHAN DRUG 343711
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
NDF-RT N0000007556
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
FDA ORPHAN DRUG 566016
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
FDA ORPHAN DRUG 338611
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
WHO-VATC QC08CA06
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
Code System Code Type Description
DRUG BANK
DB00393
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
CAS
66085-59-4
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
MERCK INDEX
M7906
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1463858
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY USP-RS
PUBCHEM
4497
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
ChEMBL
CHEMBL1428
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
ECHA (EC/EINECS)
266-127-0
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
LACTMED
Nimodipine
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
IUPHAR
2523
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
EPA CompTox
66085-59-4
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
RXCUI
7426
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY RxNorm
FDA UNII
57WA9QZ5WH
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
INN
4528
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
EVMPD
SUB09297MIG
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
WIKIPEDIA
NIMODIPINE
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
DRUG CENTRAL
1937
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
NCI_THESAURUS
C692
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
MESH
D009553
Created by admin on Fri Jun 25 21:01:52 UTC 2021 , Edited by admin on Fri Jun 25 21:01:52 UTC 2021
PRIMARY
Related Record Type Details
ENANTIOMER -> RACEMATE
TARGET -> INHIBITOR
ENANTIOMER -> RACEMATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Excretion PHARMACOKINETIC Urination
PHYSICAL
Biological Half-life PHARMACOKINETIC Elimination
PHARMACOKINETIC