title: Evaluation of succinimidoethyl and pivaloyloxyethyl esters as progenitors of methyldopa in man, rhesus monkey, dog, and rat.
abstract: The succinimidoethyl (Sm) and pivaloyloxyethyl (P) esters of methyldopa were evaluated as progenitors of the latter. Experiments in spontaneously hypertensive (SH) rats and humans demonstrated that a radioactive dose of progenitor was well absorbed. The metabolism of these progenitors appeared to be comparable in the SH rat; the urinary excretion of [3H]methyldopa was similar after oral administration of [3H]Sm or [3H]P. In humans the levels of [3H]methyldopa were higher in the urine following administration of [3H]P. Apparently Sm was more resistant than P to extrahepatic esterase action in man (and dog). In man the catechol nucleus of Sm was apparently conjugated prior to hydrolytic cleavage to release conjugated [3H]methyidopa. The progenitors possessed similar antihypertensive properties in the SH rat but preliminary results in humans suggested that Sm possessed less antihypertensive potency than P.
mesh_terms: D000328:Adult; D000818:Animals; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004285:Dogs; D005260:Female; D000882:Haplorhini; D006801:Humans; D006868:Hydrolysis; D008253:Macaca mulatta; D008297:Male; D013058:Mass Spectrometry; D008750:Methyldopa / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D013050:Spectrometry, Fluorescence
chemical_list: D008750:Methyldopa