Naltiazem

In a double blind study 8 patients with uncomplicated essential hypertension received in random order single oral doses of placebo and 10, 30 and 80 mg Ro 23-6152, a novel calcium entry blocker, on 4 different days. Patients were assessed 15 min before dosing and at several time intervals over the following 6 h. Ro 23-6152 30 and 80 mg induced a significant decrease (mean maximum 7 mmHg.1-1.min-1) in total peripheral resistance, while cardiac output, stroke volume and heart rate were slightly increased (mean maximum 0.51.min-1, 10 ml, 5 beats.min-1, respectively) but not significantly so. Systolic blood pressure decreased significantly (5 to 10 mmHg) from 0.5 to 6 h after the 80 mg dose. After the 10 and 30 mg doses the decreases in systolic pressure were not significant. Diastolic blood pressure and mean arterial blood pressure were non-significantly decreased (mean maximum 7 mmHg) after all doses. The PQ interval was also non-significantly increased by no more than 20 ms. It appears that the main hemodynamic effect of Ro 23-6152 in hypertensive patients is a decrease in peripheral resistance. The antihypertensive effect, at least in this short term study, was only modest, probably because the fall in peripheral resistance was partly compensated by an increase in cardiac output.

To compare antihypertensive effects, captopril, (+) diltiazem, the (+) and (−) enantiomers, and the racemic mixture of RO 23‐6152, 0.1–10 mg/kg, were administered intravenously to rats made hypertensive by occlusion of the abdominal aorta or by constriction of a renal artery. All drugs, with the exception of (−) RO 23‐6152, significantly decreased mean arterial pressure (MAP) and increased heart rate (HR). The (−) enantiomer of RO 23‐6152, 3 and 10 mg/kg, significantly increased MAP and decreased HR. Within the dosage range investigated (0.1–10 mg/kg), captopril, (+) diltiazem, and (+) RO 23‐6152 produced similar decreases in MAP. However, the racemate of RO 23‐6152 was significantly less effective in reducing MAP than (+) RO 23‐6152. We conclude that, with regard to antihypertensive activity, (+) RO 23‐6152 is as effective as captopril and (+) diltiazem. Furthermore, the antihypertensive effects of RO 23‐6152 are stereoselective.