Diltiazem hydrochloride is a Ca²⁺ influx inhibitor (slow channel blocker or calcium antagonist). In Vitro: 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]. In Vivo: Diltiazem produces a noncompetitive inhibition of Ca²⁺-induced contractions of depolarized rabbit aorta. Furthermore, there is a lack of parallelism between the smooth muscle effects of removal of [Ca²⁺]ex and of addition of diltiazem^[2]. Diltiazem improves the cardiac microcirculation and function in an experimental model of hyperthyroidism in rats. The treatment of hyperthyroid rats with losartan diltiazem (4.7±0.7%; P < 0.001) significantly reduces the percentage of fibrosis areas in the left ventricle ^[4]. In conscious spontaneously hypertensive rats (SHR), diltiazem dose-dependently decreases the blood pressure and increases the heart rate after intravenous administration (0.03--1 mg/kg). Oral administration of diltiazem (100 mg/kg) also reduces the blood pressure of SHR^[5].