1,4-ジヒドロ-2,6-ジメチル-4-(3-ニトロフェニル)-3,5-ピリジンジカルボン酸3-[2-[4-(ジフェニルメチル)ピペラジン-1-イル]エチル]5-メチル

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3 reports by companies from 1 notifications to the ECHA C&L Inventory.；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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Manidipine

DILI Positive

DOI:10.1016/j.drudis.2019.09.022

C - Cardiovascular system；C08 - Calcium channel blockers；C08C - Selective calcium channel blockers with mainly vascular effects；C08CA - Dihydropyridine derivatives；C08CA11 - Manidipine

QC - Cardiovascular system；QC08 - Calcium channel blockers；QC08C - Selective calcium channel blockers with mainly vascular effects；QC08CA - Dihydropyridine derivatives；QC08CA11 - Manidipine

Contraction of vascular smooth muscle is stimulated by Gq coupled receptors which produce calcium release from the sarcoplasmic reticulum. This is followed by opening of voltage dependent calcium channels and an influx of calcium into the cell ultimately producing contraction. Manidipine binds to and dissociates slowly from L- and T-type voltage dependent calcium channels on smooth muscle cells, blocking the entrance of extracellular calcium into the cell and preventing this contraction. This produces vasodilation which decreases blood pressure. Manidipine produces renal vasodilation and an increase in natriuresis. This likely contributes to the antihypertensive effect by reducing blood volume. Manidipine is selective for the vasculature and does not produce significant effects on the heart or central nervous system at clinically relevant dosages.

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.

The median Tmax is 1.5 h. Administration with food produces an 1.3-1.6-fold increase in Cmax but no change in Tmax. Manidipine does not accumulate significantly with multiple doses.

Manidipine is eliminated through extensive metabolism. 63% is eliminated in the feces and 31% in the urine as metabolites.