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  • Title: RX781094, a new potent alpha 2 adrenoceptor antagonist. In vivo and in vitro studies in the rabbit.
    Author: Hannah JA, Hamilton CA, Reid JL.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1983 Apr; 322(3):221-7. PubMed ID: 6135163.
    Abstract:
    1. RX781094 [2-(2-(1,4-benzodioxanyl))-2-imidazoline HCl] is a new alpha 2 adrenoceptor selective antagonist. Its effects on cardiovascular response "in vivo" before and after administration of alpha 1 and alpha 2 adrenoceptor agonists have been studied in conscious and anaesthetized rabbits. The affinity of RX781094 for alpha 1 and alpha 2 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 alpha 1 and alpha 2 adrenoceptor antagonists; it also caused a prolonged bradycardia. 3. Pretreatment with intravenous RX781094 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 alpha 2 adrenoceptor selective agonist guanabenz. 5. Pressor dose response curves to noradrenaline, a mixed alpha 1/alpha 2 adrenoceptor agonist were shifted to the right after RX781094 whereas those to the alpha 1 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 alpha 2 adrenoceptor antagonist effect of RX781094 at central and peripheral adrenoceptors in the rabbit.
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