Rat clonidine mydriasis model: imidazoline receptors are not involved

The clonidine mydriasis model in rats has been widely applied in preclinical research to characterize α2-adrenoceptor antagonistic properties of drugs. The present study was undertaken to pharmacologically determine if imidazoline I1 receptors are also involved in this model system. Sigmoid dose–response curves for pupillary dilation were produced in pentobarbital anesthetized rats by intravenous administration of increasing doses of agonists (guanabenz for α2-adrenoceptors, clonidine for both α2-adrenoceptors and imidazoline I1 receptors, and rilmenidine for imidazoline I1 receptors). Two antagonists (RS 79948 for α2-adrenoceptors and efaroxan for imidazoline I1 receptors) were used to antagonize the mydriasis elicited by those three agonists, with antagonistic potencies calculated. In additional experiments, we examined the effect of the selective imidazoline I1 receptor antagonist, AGN 192403, on clonidine-induced mydriasis. The results showed that pupillary response curves elicited by guanabenz, clonidine and rilmenidine were competitively antagonized by both RS 79948 (0.03–1 mg/kg) and efaroxan (0.03–1 mg/kg) in a dose-related fashion. The potencies of either antagonist against the three agonists were not significantly different. AGN 192403 (5 mg/kg) did not significantly shift the clonidine mydriasis curve. These results suggest that imidazoline I1 receptors are not functionally involved in the rat clonidine mydriasis model and support this in vivo system as a useful model for studies of α2-adrenoceptors.