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 5.9927042E11
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 1.36805758E12
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 1.17797762E12

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
Cerebral blood flow and neurologic outcome when nimodipine is given after complete cerebral ischemia in the dog.	1984 Mar	6693515
Magnetic resonance imaging in the evaluation of nimodipine-treated acute experimental focal cerebral ischemia.	1986	2980536
Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications.	1987 Nov	3323259
Nimodipine reduces the toxicity of intravenous bupivacaine in rats.	1992 Jun	1595917
Hypotensive effect of nimodipine during treatment for aneurysmal subarachnoid haemorrhage.	1995	8748871
Dose-finding study with nimodipine: a selective central nervous system calcium channel blocker on aminophylline induced seizure models in rats.	1998 Mar 15	9570719
Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice.	1999 Feb	10368871
Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines.	2001 Aug 15	11487617
Calcium channel blocker, nimodipine, for the treatment of bipolar disorder during pregnancy.	2002 Dec	12501088
Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition.	2003	14649325
Effects of blood pressure lowering in the acute phase of total anterior circulation infarcts and other stroke subtypes.	2003	12686786
Cerebral vasospasm after subarachnoid hemorrhage.	2003 Apr	12657973
A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia.	2003 Jan 23	12540643
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
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
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
Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies.	2008 Nov	19021025
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
Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid.	2013 Mar 28	23537331
Screening of a chemical library reveals novel PXR-activating pharmacologic compounds.	2015 Jan 5	25455453

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 UTC 2023` Edited by `admin` on `Fri Dec 15 18:02:29 UTC 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