2-(Benzylmethylamino)ethylmethyl-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)pyridin-3,5-dicarboxylat

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Calcium Channel Blockers; Vasodilator Agents

Pharmaceuticals

136-138 °C

136 - 138 °C

211.2 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID9046992]

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

208.67 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 1 notifications to the ECHA C&L Inventory.

Nicardipine has not been associated with significant increases in rates of elevations in serum aminotransferase or alkaline phosphatase levels, even with chronic long term therapy. Cases of idiosyncratic liver injury have not been published, although a single instance of marked serum enzyme elevations without jaundice has been reported with the use of intravenous nicardipine. Large trials of nicardipine have not mentioned liver injury, serum aminotransferase elevations or discontinuation of drug because of hepatic adverse events. Thus, clinically apparent liver injury with jaundice due to nicardipine must be rare, if it occurs at all.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

nicardipine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

C08CA04

C - Cardiovascular system

QC - Cardiovascular system

Nicardipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nicardipine is similar to other peripheral vasodilators. Nicardipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, nicardipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

Nicardipine HCl is metabolized extensively by the liver.

Nicardipine has known human metabolites that include Dehydronicardipine and De-benzylated nicardipine.

CZ5312222S

NICARDIPINE

Mechanisms of Action [MoA] - Calcium Channel Antagonists

Established Pharmacologic Class [EPC] - Dihydropyridine Calcium Channel Blocker

Chemical Structure [CS] - Dihydropyridines

Mechanisms of Action [MoA] - Cytochrome P450 3A4 Inhibitors

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.

While nicardipine is completely absorbed, it is subject to saturable first pass metabolism and the systemic bioavailability is about 35% following a 30 mg oral dose at steady state.

Nicardipine has been shown to be rapidly and extensively metabolized by the liver.

8.3 L/kg

0.4 L/hr∙kg [Following infusion]