Metabolism of dopa- 14C in the normal and α-methyldopa-treated mouse

Abstract

Intraperitoneally injected dl-3, 4-dihydroxyphenylalanine (dopa)-α- 14C was rapidly metabolized in the intact mouse; the biological half-life was approximately 15 min. Decar☐ylation constituted an important but not the only route of metabolism. One hour after the administration of dopa- 14C the following labeled catechols were found in whole mouse homogenates (concentrations expressed as a percentage of total recovered radioactivity): dopa (17.3%), dopamine (13.8%), norepinephrine (1.2%), epinephrine (0.5%), 3,4-dihydroxyphenylacetic acid (dopac) (0.8%). α-Methyldopa, injected intraperitoneally in a dose of 3.12 mg/kg, inhibited the decar☐ylation in vivo of dopa- 14C. Larger doses resulted in progressively greater inhibition; maximal response was obtained with 50 mg/kg. In mice given α-methyldopa (25 mg/kg) 30 min prior to dopa- 14C and sacrificed 1 hr later, the dopa level was increased (30.6%), and the dopamine level was reduced (3.8%). The duration in vivo of the decar☐ylase inhibitory activity of α-methyldopa in the mouse was 8 to 16 hr.