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

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
Magnetic resonance imaging in the evaluation of nimodipine-treated acute experimental focal cerebral ischemia.	1986	2980536
[Ergotism with cerebral complications. Case report and review of the literature].	1986 Apr 5	3961460
Ca2+ modulators as antidotes to imipramine and neurotransmitter toxicity.	1987 Sep	2886994
Therapeutic trial of intravenous nimodipine in patients with established cerebral vasospasm after rupture of intracranial aneurysms.	1988 Aug	3054619
Oxytocin-induced penile erection and yawning: role of calcium and prostaglandins.	1990 Mar	2339153
Quinine-induced tinnitus in rats.	1991 Oct	1910705
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
Dose-finding study with nimodipine: a selective central nervous system calcium channel blocker on aminophylline induced seizure models in rats.	1998 Mar 15	9570719
Pharmacological blockade of ERG K(+) channels and Ca(2+) influx through store-operated channels exerts opposite effects on intracellular Ca(2+) oscillations in pituitary GH(3) cells.	2000 Nov	11040061
Calcium antagonists decrease capillary wall damage in aging hypertensive rat brain.	2001 Mar-Apr	11182480
High initial blood pressure after acute stroke is associated with poor functional outcome.	2001 May	11350571
Functional properties of Cav1.3 (alpha1D) L-type Ca2+ channel splice variants expressed by rat brain and neuroendocrine GH3 cells.	2001 Oct 19	11514547
Calcium channel blocker, nimodipine, for the treatment of bipolar disorder during pregnancy.	2002 Dec	12501088
Possible involvement of dopaminergic neurotransmitter system in dichlorvos induced delayed neurotoxicity.	2002 Feb	12186780
Effects of endothelin B receptor agonists on amyloid beta protein (25-35)-induced neuronal cell death.	2002 Sep 6	12383957
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
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
The L-type calcium channel blocker nimodipine mitigates cytoskeletal proteins phosphorylation in dichlorvos-induced delayed neurotoxicity in rats.	2006 May	16635102
[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
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
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.

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