Effect of alpha-methyldopa on alpha-noradrenergic receptor binding sites in the mouse brain.
alpha-Methyldopa (alpha-MD) was administered intraperitoneally into adult male mice and its effect on alpha 1- and alpha 2-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 alpha-MD abolished the high affinity binding to alpha 2-receptor sites and only the low affinity binding was observed with lower Bmax values. A significant effect of alpha-MD on alpha 1-receptor sites was not detected even after repeated injections (200 mg/kg/day X 3). Pretreatment with fusaric acid or diethyldithiocarbamate (inhibitors of dopamine-beta-hydroxylase) exerted no influence on the actions of alpha-MD on alpha 2-receptor sites, whereas NSD-1055 (an inhibitor of dopa decarboxylase) inhibited the effects of alpha-MD. It is concluded, therefore, that alpha-methyldopamine, a decarboxylated metabolite of alpha-MD, may be responsible for the reducing effect of alpha-MD on alpha 2-receptor sites.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001958:Brocresine / Q000494:pharmacology; D003000:Clonidine / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism; D004050:Ditiocarb / Q000494:pharmacology; D005669:Fusaric Acid / Q000494:pharmacology; D008297:Male; D008750:Methyldopa / Q000494:pharmacology*; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology
D004146:Dioxanes; D008781:Methyltyrosines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D001958:Brocresine; D008750:Methyldopa; D012110:Reserpine; D004050:Ditiocarb; C031476:alpha-methyl-m-tyrosine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D005669:Fusaric Acid; D003000:Clonidine