Analysis of pupillary dilation produced by analogs of clonidine

Pupillary responses to intravenous administration of clonidine and five congeneric derivatives of clonidine were observed in anesthetized cats. All of the agents tested produced a dose-dependent mydriasis of long duration. The order of potency for these compounds was clonidine (St-155) greater than St.375 greater than St-606 greater than St-608 greater than St-91. Pretreatment with yohimbine hydrochloride (0.5 mg/kg i.v.) shifted the dose-response curve for all of the compounds tested to the right. A CNS inhibition of parasympathetic nerve activity was demonstrated for clonidine and St-375 by means of direct recordings from the postganglionic ciliary nerves. An effect of high doses of St-91 on nerve activity was also observed. These results suggest that all the analogs of clonidine tested (with the possible exception of St-91) act like clonidine to produce mydriasis by a central alpha-adrenergic inhibition of parasympathetic outflow to the eye.