Diltiazem hydrochloride (RG 83606 HCl) is a benzothiazepine calcium channel blocking agent with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.

Benzothiazepine Ca2+ antagonist diltiazem hydrochloride interacts with transmembrane segments IIIS6 and IVS6 in the α1 subunit of L-type Ca2+ channels[1]. Diltiazem causes a dose-dependent inhibiton of contractions as well as Ca2+ influx stimulated by alpha adrenoceptor activation and high-K+ depolarization. Diltiazem is roughly equally potent in inhibiting contractions induced by high-K+ and a low concentration of norepinephrine (NE)[2]. Diltiazem also inhibits the Na-dependent Ca-efflux from heart mitochondria. Both the (+)-optical isomers of the cis- and trans-forms of diltiazem inhibit Na-Ca exchange activity with comparable potency (IC50 of 10-20 μM)[3].

Diltiazem exhibits noncompetitive inhibition of calcium-induced contractions in depolarized rabbit aorta and lacks parallel effects between the removal of extracellular calcium ([Ca2+]ex) and its addition. It enhances cardiac microcirculation and function in hyperthyroid rat models, significantly reducing left ventricular fibrosis when combined with losartan (4.7±0.7%; P < 0.001). In spontaneously hypertensive rats, diltiazem lowers blood pressure and increases heart rate in a dose-dependent manner after intravenous administration (0.03--1 mg/kg) and through oral administration (100 mg/kg), demonstrating its therapeutic potential in hypertension management.