Isradipine

Practically insoluble (< 10 mg/L at 37 °C)

2.28e-01 g/L

Breast Feeding; Lactation; Antihypertensive Agents; Calcium Channel Blockers; Vasodilator Agents;

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

168-170 °C

168 - 170 °C

Danger

H301 (98%): Toxic if swallowed [Danger Acute toxicity, oral]

P260, P264, P264+P265, P270, P273, P280, P301+P316, P305+P351+P338, P319, P321, P330, P337+P317, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 51 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Isradipine

vLess-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

C - Cardiovascular system

QC - Cardiovascular system

Isradipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine result in an overall decrease in blood pressure.

Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in <i>Homo sapiens</i>: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells.

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ISRADIPINE

Mechanisms of Action [MoA] - Calcium Channel Antagonists

Established Pharmacologic Class [EPC] - Dihydropyridine Calcium Channel Blocker

Chemical Structure [CS] - Dihydropyridines

Isradipine is a Dihydropyridine Calcium Channel Blocker. The mechanism of action of isradipine 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.

Isradipine is 90%-95% absorbed and is subject to extensive first-pass metabolism, resulting in a bioavailability of about 15%-24%.

Approximately 60% to 65% of an administered dose is excreted in the urine and 25% to 30% in the feces.