Acute and chronic administration of α-methyldopa: Regional levels of endogenous and α-methylated catecholamines in rat brain

Abstract

Acute administration of α-methyldopa (200 mg kg −1 s.c.) produced a short-lived decrease in dopamine levels in 5 regions of the rat brain. Maximal dopamine depletion was 55% in the corpus striatum and over 75% in other regions and occurred 4–6 h after α-methyldopa injection; dopamine levels recovered within 12 h. Maximal noradrenaline depletion of over 80% occurred in all regions 4–24 h after α-methyldopa and after 24 h noradrenaline levels were still significantly reduced from control values. In these acute studies α-methyldopamine accumulated rapidly in amounts equal to or greater than the depleted dopamine in all regions, reaching a peak at 4 h. By contrast, α-methylnoradrenaline accumulated more slowly reaching a peak at 6–24 h and was never present in amounts greater than the depleted noradrenaline. Following chronic administration of α-methyldopa (40 mg kg −1 s.c., twice daily 5 days) there was a similar depletion of noradrenaline and dopamine to that seen in the acute studies. The depletion was associated with a much smaller accumulation of α-methyldopamine. The striking feature of these results, however, was the large accumulation of α-methylnoradrenaline in all brain regions. This probably reflects the slow turnover and resistance to degradation by monoamine oxidase of α-methylnoradrenaline.