Rat clonidine mydriasis model: imidazoline receptors are not involved.
The clonidine mydriasis model in rats has been widely applied in preclinical research to characterize alpha(2)-adrenoceptor antagonistic properties of drugs. The present study was undertaken to pharmacologically determine if imidazoline I(1) 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 alpha(2)-adrenoceptors, clonidine for both alpha(2)-adrenoceptors and imidazoline I(1) receptors, and rilmenidine for imidazoline I(1) receptors). Two antagonists (RS 79948 for alpha(2)-adrenoceptors and efaroxan for imidazoline I(1) 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 I(1) 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 I(1) receptors are not functionally involved in the rat clonidine mydriasis model and support this in vivo system as a useful model for studies of alpha(2)-adrenoceptors.
Yu
Yongxin
Y
Department of Cell Biology, University of Oklahoma College of Medicine, Oklahoma City, OK 73190, USA. yongxin-yu@ouhsc.edu
Koss
Michael C
MC
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D054755:Imidazoline Receptors; D008297:Male; D015878:Mydriasis / Q000139:chemically induced / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D054755:Imidazoline Receptors; D011955:Receptors, Drug; C410887:imidazoline I1 receptors; D010643:Phenoxybenzamine; D003000:Clonidine