Overview
- Hockerman, G.H. et al. (2000) Mol. Pharmacol. 58, 1264.
Alomone Labs Diltiazem hydrochloride inhibits L-type voltage-gated Ca2+ currents expressed in Xenopus oocytes.A. Time course of CaV1.2/α2-δ1/β1 (L-type) current inhibition by 100 µM and 1 mM Diltiazem hydrochloride (#D-135). Currents were elicited by application of voltage ramp from a holding potential of -80 mV to 0 mV (100 msec). B. Superimposed example traces of current responses before and during perfusion of 100 µM and 1 mM Diltiazem hydrochloride as indicated.
Ca2+ influx via voltage-dependent L-type Ca2+ channels (CaV1.2) found in cardiac and vascular smooth muscle initiates contraction and contributes to timing of the cardiac action potential1. CaV1.2 is sensitive to blockade by three distinct chemical classes of small-molecule drugs: dihydropyridines (DHPs), phenylalkylamines (PAAs), and benzothiazepines (BZPs).
Diltiazem hydrochloride is structurally related to benzothiazepine (BZP) Ca2+ channel blockers2. Diltiazem hydrochloride blocks CaV1.2 channels at low micromolar concentrations in both primary cardiac myocytes and heterologous expression systems. Diltiazem hydrochloride causes a modest decrease in heart muscle contractility and reduces myocardium oxygen consumption3. Research has demonstrated that diltiazem hydrochloride is able to reduce cocaine cravings in drug-addicted rats due to the effects of Ca2+ blockers on dopaminergic and glutamatergic signaling in the brain4. Diltiazem hydrochloride also enhances the analgesic effect of morphine in animal tests and reduces the development of tolerance5.
