Semotiadil recemate fumarate, the recemate of Semotiadil fumarate, is a novel antagonist of vasoselective Ca2+ channel.

Semotiadil at a concentration of 1 μM inhibits ICa by 12.4±9.7%, and at 10 μM, the inhibition increases to 25±11.0%[1]. When applied at concentrations of 0.1 μM or higher in DMSO, Semotiadil inhibits ICa in a dose-dependent manner with an IC50 of 2.0 μM at a holding potential of -100 mV. At holding potentials of -80 mV or -60 mV, Semotiadil shifts the concentration-inhibition curve and the voltage-dependent inactivation curve to the left, indicating enhanced inhibition compared with -100 mV. Analysis of ICa decay reveals two time constants, with Semotiadil at concentrations below 1 μM reducing the slow time constant without affecting the fast one. Additionally, in the recovery from ICa inactivation characterized by two time constants, Semotiadil at 1 μM prolongs the slow recovery phase. Notably, Semotiadil is more potent in inhibiting ICa when dissolved in deionized water than in DMSO[2].

Semotiadil fumarate, an innovative benzothiazine calcium antagonist, is administered either solo or concomitantly with Enalapril or trichlormethiazide to conscious, spontaneously hypertensive rats for a duration of two weeks. Notably, the antihypertensive effects of Semotiadil (10 mg/kg, p.o.) and Enalapril (5 mg/kg, p.o.) begin to manifest after the third administration, with daily progressive enhancement of effects, although efficacy diminishes before subsequent doses. A regimen comprising low-dose daily co-administration of Semotiadil and Enalapril, in particular, shows promise for sustained hypertension management.