NIMODIPINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H26N2O7
Molecular Weight	418.4403
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COCCOC(=O)C1=C(C)NC(C)=C(C1C2=CC(=CC=C2)[N+]([O-])=O)C(=O)OC(C)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	418.4403
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2663415
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel 92 Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2565839	Antagonist 2778		0.27 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Subarachnoid hemorrhage 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018869s014lbl.pdf	Primary	Approved 8429	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 1988
Subarachnoid hemorrhage 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203340lbl.pdf	Primary	Approved 8429	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 2013
Subarachnoid hemorrhage 10 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0a13a26-b9dc-4ed1-b2c4-46e14fb60bfc	Primary	Approved 8429	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 2007

C_max

Value	Dose	Co-administered	Analyte	Population
20 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8249618	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7962672	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

Value	Dose	Co-administered	Analyte	Population
100 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8249618	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7962672	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8249618	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7962672	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018869s014lbl.pdf			NIMODIPINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/3283595/	unhealthy, 47 (21-63) n = 38 Health Status: unhealthy Condition: subarachnoid haemorrhage Age Group: 47 (21-63) Sex: M+F Population Size: 38 Sources: https://pubmed.ncbi.nlm.nih.gov/3283595/	Other AEs: Death... Other AEs: Death (grade 5, 4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/3283595/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203340s011lbl.pdf	unhealthy, adult n = 4 Health Status: unhealthy Condition: subarachnoid haemorrhage Age Group: adult Sex: unknown Population Size: 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203340s011lbl.pdf	Other AEs: Blood pressure decreased... Other AEs: Blood pressure decreased (50%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203340s011lbl.pdf
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: https://pubmed.ncbi.nlm.nih.gov/3725134/	unhealthy, adult n = 120 Health Status: unhealthy Condition: subarachnoid hemorrhage Age Group: adult Sex: M+F Population Size: 120 Sources: https://pubmed.ncbi.nlm.nih.gov/3725134/	Other AEs: Death... Other AEs: Death (grade 5, 7 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/3725134/

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/3283595/	unhealthy, 47 (21-63) n = 38 Health Status: unhealthy Condition: subarachnoid haemorrhage Age Group: 47 (21-63) Sex: M+F Population Size: 38 Sources: https://pubmed.ncbi.nlm.nih.gov/3283595/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203340s011lbl.pdf	unhealthy, adult n = 4 Health Status: unhealthy Condition: subarachnoid haemorrhage Age Group: adult Sex: unknown Population Size: 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203340s011lbl.pdf
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: https://pubmed.ncbi.nlm.nih.gov/3725134/	unhealthy, adult n = 120 Health Status: unhealthy Condition: subarachnoid hemorrhage Age Group: adult Sex: M+F Population Size: 120 Sources: https://pubmed.ncbi.nlm.nih.gov/3725134/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699	P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://link.springer.com/article/10.1007/s11095-005-8384-4	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/7620235/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22001996/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2290231/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7575	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7575
ChemicalBook	CB1398087	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1398087
MolPort	MolPort-001-840-190	https://www.molport.com/shop/molecule-link/MolPort-001-840-190
Selleck Chemicals	Nimodipine(Nimotop)	http://www.selleckchem.com/products/Nimodipine(Nimotop).html
eMolecules	592477	https://www.emolecules.com/cgi-bin/more?vid=592477

PubMed

Title	Date	PubMed
Effect of nimodipine (Bay e 9736) on postischaemic cerebrovascular reactivity, as revealed by measuring regional cerebral blood flow (rCBF).	1982	7102420
Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage.	1983 Mar 17	6338383
Cerebral blood flow and neurologic outcome when nimodipine is given after complete cerebral ischemia in the dog.	1984 Mar	6693515
Implications of nimodipine prophylaxis of cerebral vasospasm on anesthetic management during intracranial aneurysm clipping.	1985 Feb	3881564
Blood pressure and heart rate during treatment with nimodipine in patients with subarachnoid hemorrhage.	1985 May	4010871
[Ergotism with cerebral complications. Case report and review of the literature].	1986 Apr 5	3961460
Nimodipine-treated subarachnoid hemorrhage associated with acute pseudo-obstruction of the colon.	1987 Aug	3603356
Effects of nimodipine on the production of thromboxane A2 following total global cerebral ischemia.	1988 Sep	3404240
HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists.	1990 Apr 20	2326646
Nimodipine pretreatment improves cerebral blood flow and reduces brain edema in conscious rats subjected to focal cerebral ischemia.	1990 Nov	2211883
Quinine-induced tinnitus in rats.	1991 Oct	1910705
Nimodipine reduces the toxicity of intravenous bupivacaine in rats.	1992 Jun	1595917
Pulmonary vasoconstriction following intravenous nimodipine.	1992 May	1599066
Effects of the combination of ketoconazole and calcium channel antagonists against Candida albicans in vitro.	1993 Jul	8369013
Sinus arrest after nimodipine treatment for a head injury.	1994	8061545
Cocaine toxicity and the calcium channel blockers nifedipine and nimodipine in rats.	1994 Jan-Feb	8163794
Hypotensive effect of nimodipine during treatment for aneurysmal subarachnoid haemorrhage.	1995	8748871
Preliminary study on controlled hypotension induced by nimodipine in craniocerebral surgery.	1995 Jun	7555250
Effect of calcium channel blockers on withdrawal syndrome of lorazepam in rats.	1996 Jun	8707372
Haemodynamic effects of intravenous nimodipine following aneurysmal subarachnoid haemorrhage: implications for monitoring.	1997 May	9165970
Dose-finding study with nimodipine: a selective central nervous system calcium channel blocker on aminophylline induced seizure models in rats.	1998 Mar 15	9570719
Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition.	2003	14649325
Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro.	2003 Aug	12730611
Severe myocardial depression following intravenous nimodipine for aneurysmal subarachnoid haemorrhage.	2004 Jul	15168009
Easily reversible hypoxemia and hypotension induced by nimodipine.	2004 Oct	15359206
Use of phenytoin and other anticonvulsant prophylaxis in patients with aneurysmal subarachnoid hemorrhage.	2005 Dec	16269628
Antioxidant effect of nimodipine in young rats after pilocarpine-induced seizures.	2005 Sep	16115668
Ion changes in spreading ischaemia induce rat middle cerebral artery constriction in the absence of NO.	2005 Sep	15901647
Effect of nimodipine on outcome in patients with traumatic subarachnoid haemorrhage: a systematic review.	2006 Dec	17110283
Reversible cerebral angiopathy: efficacy of nimodipine.	2006 Dec	17063316
Low dose hydroxylated PCB induces c-Jun expression in PC12 cells.	2006 Mar	16300829
The L-type calcium channel blocker nimodipine mitigates cytoskeletal proteins phosphorylation in dichlorvos-induced delayed neurotoxicity in rats.	2006 May	16635102
Protective effect of adenosine reuptake inhibitors in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes.	2007	17377417
[Effect of nimodipine on mechanisms of HL-60 cell apoptosis induced by cytarabine].	2007 Feb	17490525
L-type calcium channel blockade on haloperidol-induced c-Fos expression in the striatum.	2007 Nov 9	17913375
Amphetamine-induced anxiety-related behavior in animal models.	2007 Nov-Dec	18195452
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	18178321
A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity.	2008 Mar	18250364
Ammonia inhibits the C-type natriuretic peptide-dependent cyclic GMP synthesis and calcium accumulation in a rat brain endothelial cell line.	2008 May	18222015
Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies.	2008 Nov	19021025
Protective effect of L-type calcium channel blockers against haloperidol-induced orofacial dyskinesia: a behavioural, biochemical and neurochemical study.	2008 Sep	18363098
Chloride channels as drug targets.	2009 Feb	19153558
Cell death induced by zinc and cadmium is mediated by clusterin in cultured mouse seminiferous tubules.	2009 Jul	19288494
Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage.	2009 Sep	19844625
Organophosphorus-induced delayed neuropathy: a simple and efficient therapeutic strategy.	2010 Feb 1	19914363
Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening.	2011 Feb	21068194
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	22974967
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	22700542
Nephroprotective effect of calcium channel blockers against toxicity of lead exposure in mice.	2013 Apr 26	23428833
Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid.	2013 Mar 28	23537331

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 Dec 15 18:02:29 GMT 2023` Edited by `admin` on `Fri Dec 15 18:02:29 GMT 2023`
Record UNII	57WA9QZ5WH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NIMODIPINE

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 [USP IMPURITY]

Common Name

English

NIMODIPINE AP

Brand Name

English

ADMON

Brand Name

English

NIMODIPINE [ORANGE BOOK]

Common Name

English

nimodipine [INN]

Common Name

English

NIMODIPINE [JAN]

Common Name

English

NEMOTAN

Brand Name

English

Nimodipine [WHO-DD]

Common 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