Isradipine

371.39

371.39

1308068-626-2

759892

DTXSID4023179

C - Cardiovascular system

2934990002

104

4.3

yellow solid

1.3±0.1 g/cm3

168-170 °C

501.9ºC at 760 mmHg

257.4±32.9 °C

1.566

H2O: Practically insoluble (< 10 mg/L at 37 °C);DMSO: ~26 mg/mL

2-8°C

NONH for all modes of transport

3

22-24/25

P260, P264, P270, P273, P280, P301+P310, P305+P351+P338, P314, P321, P330, P337+P313, P391, P405, P501

H301

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P260, P264, P270, P273, P280, P301+P310, P305+P351+P338, P314, P321, P330, P337+P313, P391, P405, and P501|Aggregated GHS information provided by 51 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Symptoms of overdose include lethargy, sinus tachycardia, and transient hypotension. Significant lethality was observed in mice given oral doses of over 200 mg/kg and rabbits given about 50 mg/kg of isradipine. Rats tolerated doses of over 2000 mg/kg without effects on survival.

95%

For the management of mild to moderate essential hypertension. It may be used alone or concurrently with thiazide-type diuretics.

Isradipine is a second generation calcium channel blocker that is used to treat hypertension. Isradipine is associated with a low rate of serum enzyme elevations during therapy, but has not been linked convincingly to instances of clinically apparent liver injury.

Cardiovascular Agents

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.

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. (See all compounds classified as Antihypertensive Agents.)|A class of drugs that act by selective inhibition of calcium influx through cellular membranes. (See all compounds classified as Calcium Channel Blockers.)|Drugs used to cause dilation of the blood vessels. (See all compounds classified as Vasodilator Agents.)

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.

Hepatic. Completely metabolized prior to excretion and no unchanged drug is detected in the urine.

8 hours

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 Homo sapiens: 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.

Dynacirc

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals