RX781094, a new potent ?2 adrenoceptor antagonist

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Abstract
Summary 1. RX781094 [2-(2-(1,4-benzodioxanyl))-2-imidazoline HCl] is a new α2 adrenoceptor selective antagonist. Its effects on cardiovascular response “in vivo” before and after administration of α1 and α2 adrenoceptor agonists have been studied in conscious and anaesthetized rabbits. The affinity of RX781094 for α1 and α1 adrenoceptors has been investigated “in vitro” in radioligand binding studies. 2. Intravenous injection of RX781094 caused an immediate short lived pressor response which was attenuated by α1 and α2 adrenoceptor antagonists; it also caused a prolonged bradycardia. 3. Pretreatment with intravenous RX 781094 inhibited the hypotensive response to both intravenous and intracisternal clonidine in a dose dependent manner. 4. RX781094 also showed a dose dependent inhibition of the acute pressor response to the α2 adrenoceptor selective agonist guanabenz. 5. Pressor dose response curves to noradrenaline, a mixed α1/α2 adrenoceptor agonist were shifted to the right after RX781094 whereas those to the α1 adrenoceptor agonist phenylephrine were unchanged. 6. RX781094 was more effective at displacing specifically bound 3H clonidine than 3H prazosin in membrane preparations from rabbit brain. 7. These observations are consistent with a selective α2 adrenoceptor antagonist effect of RX781094 at central and peripheral adrenoceptors in the rabbit.