Effect of α-Methyldopa on α-Noradrenergic Receptor Binding Sites in the Mouse Brain

Abstract

α-Methyldopa (α-MD) was administered intraperitoneally into adult male mice and its effect on α₁- and α₂-noradrenergic receptor binding sites in the brain was investigated, using [³H]WB-4101 and [³H]clonidine, respectively. A single injection of 50–200 mg/kg α-MD abolished the high affinity binding to α₂-receptor sites and only the low affinity binding was observed with lower B_max values. A significant effect of α-MD on α₁-receptor sites was not detected even after repeated injections (200 mg/kg/day × 3). Pretreatment with fusaric acid or diethyldithiocarbamate (inhibitors of dopamine-β-hydroxylase) exerted no influence on the actions of α-MD on α₂-receptor sites, whereas NSD-1055 (an inhibitor of dopa decarboxylase) inhibited the effects of α-MD. It is concluded, therefore, that α-methyldopamine, a decarboxylated metabolite of α-MD, may be responsible for the reducing effect of α-MD on α₂-receptor sites.