Antihypertensive effects of a novel calcium antagonist, semotiadil fumarate (SD-3211), alone and in combination with enalapril or trichlormethiazide in spontaneously hypertensive rats

Semotiadil fumarate, a novel benzothiazine calcium antagonist, was given alone or in combination with either enalapril or trichlormethiazide to conscious, spontaneously hypertensive, rats daily for 2 weeks. Systolic blood pressure and heart rate were recorded 24 h before the start of the regimen and then every 2 and 24 h after the 1st, 3rd, 7th, 10th and 14th doses. When given alone, the antihypertensive effects of semotiadil (10 mg/kg, p.o.) and enalapril (5 mg/kg, p.o.) first became apparent after the 3rd dose and thereafter the effects appeared to develop daily although this effect had waned by the time of the next dose. When given in combination, however, these drugs appeared to potentiate each other and after the 7th dose, the antihypertensive effect persisted. Trichlormethiazide (30 mg/kg, p.o.) alone failed to exert any significant antihypertensive effect and in combination was not always additive to that of semotiadil. In contrast to the effect on blood pressure, the heart rate remained resistant to all these drugs. These results indicate that combined daily dosing of semotiadil, especially with enalapril, each at relatively low doses may be able to control hypertension in a continuous manner.