DIFFERENTIAL COMPETITION BY L-ALPHA-METHYLDOPA METABOLITES FOR ADRENERGIC-RECEPTORS IN RAT FOREBRAIN

Abstract

The capacity of a series of intraneuronal metabolites of L-.alpha.-methyldopa to compete for .alpha.1 ([3H]prazosin), .alpha.2 ([3H] clonidine) and .beta.-([3H]dihydroalprenolol) receptor binding in rat forebrain was studied. Each metabolite studied had a unique order of activity at each receptor. Evidently, (-)-erythro-.alpha.-methylnorepinephrine and (-)-erythro-.alpha.-methylepinephrine compete with high affinity for .alpha.2 receptors, supporting the suggestion that .alpha.2 receptors mediate hypotensive effects of L-.alpha.-methyldopa. These metabolites of L-.alpha.-methyldopa competed with high potency for .beta.1 receptors in forebrain, and (-)-erythro-.alpha.-methylepinephrine was more potent than (-)-epinephrine, (-)-norepinephrine and (-)-erythro-.alpha.-methylnorepinephrine in competing for .beta.2 receptors on human lymphocytes. Evidently .beta.2 receptor stimulation may be important in determining the net effects of L-.alpha.-methyldopa. L-.alpha.-Methyldopa metabolites were much less potent than (-)-epinephrine and (-)-norepinephrine in competition for .alpha.1 receptors. (.+-.)-.alpha.-Methyldopamine was less potent than other L-.alpha.-methyldopa metabolites at all 3 receptors, suggesting that it is unlikely to be an important hypotensive metabolite of L-.alpha.-methyldopa.