Selective stimulation of central alpha-autoreceptors following treatment with alpha-methyldopa and FLA 136.
1. The accumulation of normetanephrine in the rat brain induced by the monoamine oxidase inhibitor nialamide was inhibited following alpha-methyldopa and 4-amino-3-(2,6-dichlorobenzylidenehydrazino)-1,2,4-triazole (FLA 136). It was not changed following alpha-methylmetatyrosine despite a greater disappearance of noradrenaline than after alpha-methyldopa. The alpha-adrenoreceptor blocking agent yohimbine increased the nialamide-induced accumulation of normetanephrine and completely antagonized the actions of alpha-methyldopa and FLA 136, indicating that the effects of the two drugs are due to stimulation of alpha-adrenoreceptors. 2. The flexor reflex activity of spinalized rats was not influenced by alpha-methyldopa and alpha-methylmetatyrosine at the doses used in the biochemical experiments, as previously found for FLA 136, indicating no stimulation of classical, postsynaptic, central alpha-adrenoreceptors. 3. The biochemical effects of alpha-methyldopa and FLA 136 might be caused by stimulation of alpha-autoreceptors on the cell bodies and the nerve terminals of noradrenaline neurons. A similar mechanism might be involved in the hypotension reported by other investigators following these drugs.
D000316:Adrenergic alpha-Agonists; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D008750:Methyldopa / Q000494:pharmacology*; D009526:Nialamide / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D009647:Normetanephrine / Q000494:pharmacology; D051381:Rats; D012018:Reflex / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D014230:Triazoles; D009647:Normetanephrine; D015016:Yohimbine; C014891:FLA-136; D008750:Methyldopa; D009526:Nialamide; D009638:Norepinephrine