Comparative effects of urapidil, prazosin, and clonidine on ligand binding to central nervous system receptors, arterial pressure, and heart rate in experimental animals.

We studied the effects of urapidil, clonidine, and prazosin on ligand binding to central nervous system receptors in rats and on arterial pressure and heart rate in chloralose-anesthetized cats. Ligand binding studies indicated that urapidil had 90 times greater affinity for alpha 1 than for alpha 2 adrenergic receptors. Administration of urapidil (129 micrograms) into the cerebroventricles of cats revealed no effect after lateral ventricle injection, a decrease of 9.7 +/- 3.0 mm Hg after fourth ventricle injection, and an increase of 10.8 +/- 2.2 mm Hg after restriction of the drug in the forebrain ventricles. Clonidine (30 micrograms) produced hypotension and bradycardia after injection into the lateral ventricle. Prazosin was ineffective after cerebroventricular injection. Intravenous administration of 0.22, 0.67, and 2.00 mg/kg urapidil produced dose-dependent decreases in arterial pressure that were associated with blockade of alpha 1 adrenergic receptors. Intravenous administration of prazosin elicited the same response. Clonidine (10 micrograms/kg, intravenously produced an initial increase in arterial pressure that was unaffected by pretreatment with urapidil or prazosin. These results suggest that urapidil produces hypotension by an action on the peripheral vasculature and in the hindbrain. The peripheral effect involves blockade of alpha 1 adrenoceptors.