INVITRO AND INVIVO STUDIES ON THE EFFECTS OF THE ALPHA-ADRENOCEPTOR BLOCKER IP/66 (1-(2-ETHOXY-2-(3'-PYRIDYL)ETHYL)-4-(2'-METHOXY-PHENYL)PIPERAZINE) ON URETHRAL TONE IN RATS

IP/66 (1-(2-ethoxy-2-(3'-pyridyl)ethyl)-4-(2'-methoxy-phenyl)piperazine is a newly synthetized and stereoselective alpha-adrenoceptor blocking drug. This compound exhibits preferential blocking activity in postjunctional as compared to prejunctional alpha-adrenergic responses. Furthermore, IP/66 inhibits phenylephrine-induced motor response in human and rat prostatic tissue and phenylephrine-, DMPP- and EFS-induced motor responses in rat urethral tissues, being equieffective or even more potent than prazosin. Like prazosin, intravenous administration of IP/66, at doses at which no hypotensive effect is observed, induces a marked inhibition of phenylephrine or DMPP-induced increase in urethral perfusion pressure, in anaesthetized pithed rats. Finally, IP/66 administration exerts beneficial effects in animals with surgically- or pharmacologically-induced urethral outflow obstruction. As a whole, the pharmacodynamic profile of IP/66 is promising and this drug might be proposed for clinical setting evaluating its efficacy for the treatment of lower urinary tract dysfunctions.