Antihypertensive activity of tibalosine (CP 804 S) in the rat. Possible involvement of a central alpha 1-adrenergic receptor blockade.

The effect of tibalosine (CP 804 S) on systolic blood pressure and heart rate of unanaesthetized normotensive, spontaneously hypertensive (SHR) and DOCA-salt and Goldblatt hypertensive rats has been examined. After a single oral dose, tibalosine (1.9 to 15 mg/kg) elicited dose-dependent reductions in blood pressure in the four models tested. These reductions are accompanied by a tachycardia except in the SHR where no variation in heart rate is observed. The same result is obtained in SHR after oral, i.v. or i.c.v. administration. After repeated treatment (9 to 14 weeks), the blood pressure lowering effect of tibalosine (10 mg/kg, p.o.) is observed only in hypertensive rats. No variation in heart rate is observed in normotensive, DOCA-salt and Goldblatt rats. A significant bradycardia is observed in the SHR. The antihypertensive effect of tibalosine in SHR is suppressed by naloxone, like that of clonidine and unlike that of prazosin. The present study suggests that the antihypertensive activity of tibalosine is at least partly centrally mediated.