Studies on the mechanism of methyl-dopa-induced mydriasis in the cat.
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.
D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D002415:Cats; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008750:Methyldopa / Q000494:pharmacology*; D009184:Mydriatics / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D006834:Hydrazines; D009184:Mydriatics; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D015016:Yohimbine; D008750:Methyldopa; C004297:3-hydroxybenzylhydrazine; D011224:Prazosin