The effect of acute alpha-methyldopa administration on catecholamine levels in anterior hypothalamic-preoptic and medullary nuclei in rat brain.

α-Methyldopa administration to rats (200mg kg^?1 s.c.) produced a marked reduction in levels of noradrenaline and dopamine in anterior hypothalamic-preoptic nuclei implicated in catecholamine-mediated cardiovascular-inhibitory functions. Similar effects were observed in medullary nuclei, including the n. tractus solitarius which has been postulated as a site for the hypotensive action of α-methyldopa. The metabolite, α-methyldopamine, accumulated rapidly and 4hr after drug administration levels were higher in most nuclei than in either the medulla oblongata or hypothalamus as a whole, suggesting greater uptake of α-methyldopa into these specific areas. This was also reflected by higher levels of α-methylnoradrenaline in the nuclei than in the gross regions. The time course of accumulation and disappearance of α-methylnoradrenaline in the n. tractus solitarius differed from that in the anterior hypothalamic-preoptic nuclei and more closely correlated with the reported time course of the hypotensive effect of α-methyldopa. However, the action of this metabolite in both areas may contribute to the fall in blood pressure.