ニモジピン

3.05

2.7

125

125 °C

202.11 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；182.83 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；198.78 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；194.6 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

197.8 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

This chemical does not meet GHS hazard criteria for 1.5% (1 of 67) of reports.

Warning

H315 (35.8%): Causes skin irritation [Warning Skin corrosion/irritation]；H361 (37.3%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]；H373 (58.2%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

P203, P260, P264, P280, P302+P352, P318, P319, P321, P332+P317, P362+P364, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 67 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 1 of 67 reports by companies.；There are 6 notifications provided by 66 of 67 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Nimodipine is usually well-tolerated orally, but its use correlates with some side effects related to its use as a vasodilator. The most common adverse effects of this medication include headache, vertigo, flushing, nausea, diarrhea, pedal edema, rash, and palpitations.；Acute colonic pseudo-obstruction (Ogilvie syndrome) has been documented in patients administered oral nimodipine. Internal carotid and middle cerebral artery narrowing leading to cerebral infarction have been reported 5 months after intraventricular administration of sustained-release nimodipine.；Drug-Drug Interactions；Nimodipine is metabolized by the cytochrome P450 3A4 system. Drugs that inhibit this enzyme can cause elevated plasma concentrations of nimodipine. These drugs include macrolide antibiotics (eg, erythromycin, clarithromycin, and telithromycin), protease inhibitors (eg, ritonavir, indinavir, nelfinavir, and saquinavir), "-azole" antimycotics (eg, ketoconazole, voriconazole, itraconazole), antidepressants (eg, nefazodone, fluoxetine), quinupristin/dalfopristin, cimetidine, and valproic acid. Grapefruit juice also inhibits this cytochrome system and should be avoided by any patient taking nimodipine.；Medications including carbamazepine, phenobarbital (phenobarbitone), and phenytoin are CYP3A4 inducers. Concomitant administration of any of these medications enhances nimodipine's metabolism. This process reduces nimodipine's serum concentration and increases the likelihood of treatment failure.

Signs and Symptoms of Overdose；Acute toxicity due to overdose can cause significant hypotension, cardiac arrhythmia, nausea, and vomiting. Refractory, nimodipine-induced vasoplegia may occur.；Management of Overdose；No specific antidote is available. Overdoses are managed initially by discontinuing nimodipine and treating symptoms. Gastric lavage may be considered if the toxicity is due to oral intake, and charcoal can be administered in emergencies. Hypotension is managed with inotropes, and arrhythmias are managed by cardiologists and emergency department staff. Since nimodipine is highly protein-bound, dialysis is unlikely to be beneficial.Recent case reports suggest hydroxocobalamin as a potential rescue therapy for nimodipine-induced refractory vasoplegia.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Nimodipine

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

◉ Summary of Use during Lactation；Based on limited data, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants.；◉ Effects in Breastfed Infants；Relevant published information was not found as of the revision date.；◉ Effects on Lactation and Breastmilk；Relevant published information was not found as of the revision date.

C08CA06

C - Cardiovascular system；C08 - Calcium channel blockers；C08C - Selective calcium channel blockers with mainly vascular effects；C08CA - Dihydropyridine derivatives；C08CA06 - Nimodipine

QC - Cardiovascular system；QC08 - Calcium channel blockers；QC08C - Selective calcium channel blockers with mainly vascular effects；QC08CA - Dihydropyridine derivatives；QC08CA06 - Nimodipine

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.

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. By specifically binding to L-type voltage-gated calcium channels, nimodipine inhibits the calcium ion transfer, resulting 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.

Hepatic metabolism via CYP 3A4.

Nimodipine has known human metabolites that include 2,6-Dimethyl-4-(3-nitrophenyl)-5-propan-2-yloxycarbonyl-1,4-dihydropyridine-3-carboxylic acid, Unii-96S4GG1upr, and Dehydro nimodipine.

57WA9QZ5WH

NIMODIPINE

Mechanisms of Action [MoA] - Calcium Channel Antagonists

Established Pharmacologic Class [EPC] - Dihydropyridine Calcium Channel Blocker

Chemical Structure [CS] - Dihydropyridines

Nimodipine is a Dihydropyridine Calcium Channel Blocker. The mechanism of action of nimodipine is as a Calcium Channel Antagonist.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

A class of drugs that act by selective inhibition of calcium influx through cellular membranes.

Drugs used to cause dilation of the blood vessels.

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.

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.