化合物信息

Drug Groups

approved

Description

Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. It is structurally related to felodipine, nifedipine, and nimodipine and is the most potent calcium-channel blocking agent of the DHP class. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Isradipine may be used to treat mild to moderate essential hypertension.

Indication

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

Pharmacology

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.

Toxicity

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.

Affected Organisms

Biotransformation

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

Absorption

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

Half Life

8 hours

Protein Binding

95%

Elimination

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

References

External Links