α‐Methyldopa produces mydriasis in the rat by stimulation of CNS α2‐adrenoceptors

Abstract

1. The effects of i.v. administration of alpha-methyldopa (MD) on rat pupil diameter were investigated. All experiments were carried out in rats in which vagosympathetic nerve trunks were sectioned bilaterally at the cervical level. 2. In anaesthetized rats MD produced a marked dose-related increase in pupil diameter. The onset of pupillary response to MD was gradual and reached maximal levels 2-3 h after administration. 3. Pretreatment with alpha 2-adrenoceptor antagonists yohimbine (1.5 mg kg-1, i.v.) or idazoxan (0.5 mg kg-1, i.v.) blocked the pupillary response to MD. In contrast, the alpha 1-antagonists prazosin (1.0 mg kg-1, i.v.) and phenoxybenzamine (1.5 mg kg-1, i.v.) did not significantly alter the pupillary effects of MD. 4. Selective enzymatic blockade with 3-hydroxy-benzyl-hydrazine (NSD-1015; 25 mg kg-1, i.p.), a dopa-decarboxylase inhibitor, as well as bis (4-methyl-homopiperazinyl-thiocarbonyl) disulphide (FLA-63, 5.0 mg kg-1, i.p.), a dopamine-beta-hydroxylase inhibitor, prevented the mydriatic effect of MD. 5. The above findings support the hypothesis that MD produces a clonidine-like CNS mydriasis in the rat. This effect appears to be mediated primarily by the MD metabolite, alpha-methylnoradrenaline. 6. These results indicate that MD produces mydriasis in the rat by a CNS action. The mydriatic action of MD appears to be produced by its metabolite alpha-methylnoradrenaline which in turn stimulates CNS postsynaptic alpha 2-adrenoceptors.