In vivo pharmacological activity of r 47 243 in rat: A comparison with putative α2‐adrenoceptor antagonists

Abstract The study examined the effects of R 47 243 and its (‐)‐ and (+)‐isomers as well as those of the putative α2‐antagonists yohimbine, piperoxan, CGS 7225 A, and idazoxan at 1‐ to 24‐hr time intervals after oral administration in rats. The experiments determined the antagonism produced by these compounds of the loss of the righting reflex (LRR) and of the exophthalmia (EXO) induced by intraperitoneal injection of 20 mg/kg of xylazine. Antagonism of LRR constitutes an in vivo measure of drug antagonist effects at CNS receptors that mediate behavioral depression produced by putative α2‐agonists; antagonism of EXO offers an in vivo measure of α1‐antagonist activity. More so than idazoxan or any of the other putative α2‐antagonists tested, R 47 243 appeared to be a potent, long acting, and specific antagonist; it also acted as a full antagonist rather than as a partial agonist and showed excellent oral absorption.