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 α-methyldopa and 4-amino-3-(2,6-dichlorobenzylidenehydrazino)-1,2,4-triazole (FLA 136). It was not changed following α-methylmetatyrosine despite a greater disappearance of noradrenaline than after α-methyldopa. The α-adrenoreceptor blocking agent yohimbine increased the nialamide-induced accumulation of normetanephrine and completely antagonized the actions of α-methyldopa and FLA 136, indicating that the effects of the two drugs are due to stimulation of α-adrenoreceptors. 2. The flexor reflex activity of spinalized rats was not influenced by α-methyldopa and α-methylmeta-tyrosine at the doses used in the biochemical experiments, as previously found for FLA 136, indicating no stimulation of classical, postsynaptic, central α-adrenoreceptors. 3. The biochemical effects of α-methyldopa and FLA 136 might be caused by stimulation of α-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. © 1979 Springer-Verlag.