Effects of Methyldopa Metabolites on Amine Transmitters and Adrenergic Receptors in Rat Brain

Abstract

Studies of catecholamine concentrations in defined nuclei from the anterior hypothalamic-preoptic regions and the medulla oblongata, known to contribute to cardiovascular control, were measured following acute or chronic methyldopa administration. These studies indicated that methyldopa was enzymatic-ally converted to methyldopamine and methylnorepinephrine, and in some areas to methylepinephrine which replaced endogenous epinephrine. The predominant metabolite was methylnorepinephrine, which accumulated in concentrations higher than endogenous norepinephrine levels. (-)Methylnorepinephrine was found to be 6 times more potent and 75 times more selective for α2-adrenergic receptors than (-) norepinephrine, and it is suggested that this α2-adrenergic receptor action, particularly in the nucleus tractus solitarius, contributes to a major part of the antihypertensive effect of methyldopa.