Antihypertensive activity and interaction with alpha-adrenoceptors of tibalosine ([1-(2, 3-dihydro-5-benzo-(b)-thienyl)-2-(4-phenyl-butylamino)-1-propanol], CP 804 S) in rat and cat preparations.

The antihypertensive and hypotensive effects and the interaction with postjunctional alpha 1- and alpha 2-adrenoceptors of tibalosine were studied in various animal preparations. Tibalosine (CP 804 S, 1-10 mg/kg) elicited dose-dependent reductions in blood pressure upon i.v., oral or i.p. administration in conscious SEHR, in pentobarbitone-anaesthetized, normotensive rats, in chloralose-anaesthetized cats and in vasopressin-supported pithed normotensive rats. These reductions were not influenced by naloxone. Infusion via the vertebral artery of chloralose-anaesthetized cats (1 mg/kg) elicited a modest, centrally mediated reduction of blood pressure, which could be antagonized by yohimbine or naloxone, but not by prazosin. Intracerebroventricular application of tibalosine (3-300 micrograms/kg) to conscious SHR elicited pressor responses. In pithed normotensive rats, tibalosine inhibited the pressor responses to i.v. cirazoline (pA2 = 5.47 +/- 0.17), but not to those by i.v. B-HT 920 Tibalosine selectively displaced [3H]-prazosin from its specific binding site in rat isolated brain membranes. The present study identifies tibalosine as a highly selective alpha 1-adrenoceptor antagonist, 700-1000 times less potent than prazosin. The antihypertensive effect of tibalosine is most likely to be attributed to blockade of alpha 1-adrenoceptors in the peripheral circulation.