Studies on the mechanism of methyl-Dopa-induced mydriasis in the cat

Abstract

alpha-methyl-Dopa (10–100 mg/kg, i.v.) produced a dose-dependent mydriasis in cats anaesthetized with pentobarbital (30 mg/kg, i.p.). The onset was gradual, reaching a maximum plateau in 2–2.5 h. Intracerebroventricular administration of 1 or 3 mg of alpha-methyl Dopa (MD) also produced pupillary dilation with a similar time course. These dosages were without effect when given intravenously. Pretreatment with the alpha ₂-adrenoceptor antagonist, yohimbine (0.5 mg/kg, i.v.), blocked the pupillary response to MD. The alpha ₁-adrenoceptor antagonist, prazosin (1.0 mg/kg, i.p.), was ineffective. Selective enzymatic blockade with 3-hydroxy-benzyl-hydrazine (NSD-1015; 25 mg/kg, i.p.), a Dopa-decarboxylase enzyme inhibitor, as well as with bis (4-methyl-homopiperazinyl-thiocarbonyl) disulfide (FLA-63; 2.5 mg/kg, i.p.), a dopamine-beta-hydroxylase blocker, prevented the mydriatic effect of MD. These results support the hypothesis that MD produces a clonidine-like, CNS mediated mydriasis in the cat, primarily by action of its metabolite alpha-methyl-noradrenaline acting on alpha ₂-adrenoceptors.