Methyldopa for Treatment of Hypertension

Abstract

ABORTION RATEMEDICALBJOURNsL 295 cause of spontaneous abortion, which still remains unknown. Although only six of the abortuses have been recovered for detailed study, four of them were grossly abnormal. The abnormalities were distributed evenly between patients who received either solution A or solution B. It remains to be determined whether these abnormalities are environmentally or genetically determined.It has taken over three years to collect the 50 cases published in this paper, and because of this relatively small number the investigation will continue to ensure that small, but perhaps ultimately significant, differences do not escape detection. (Goldenberg et al., 1948), although evidence for increased production of these adrenergic amines is absent in most forms of hypertension (von Euler, 1956). SummaryIrrespective of the exact role of catecholamines in hypertension, control of their endogenous production might provide a means of lowering blood-pressure. Methyldopa is a compound shown in vitro to be an effective inhibitor of the decarboxylation of dihydroxyphenylalanine, a precursor of catecholamines (Sourkes, 1954). This effect was subsequently confirmed pharmacologically (Reichel and Dengler, 1958). Inhibition of 5-hydroxytryptophan, tyrosine, and tryptophan decarboxylation was also demonstrated (Oates et al., 1960). On administration of methyldopa to hypertensive patients it immediately proved to be an antihypertensive agent (Oates et al., 1960). This warranted a more extensive study in order to assess its value either as a sole agent or in combination with other drugs in the treatment of hypertension. Possible toxic effects of the drug on the liver, kidneys, and blood picture, and certain aspects of the catecholamine metabolism during administration of methyldopa, have been studied. Materials and MethodsTwenty-eight subjects with persistent hypertension were selected for this study, their ages ranging from 22 to 72 (average 46 Twenty-three hypertensive patients received the drug during their stay in hospital, their blood-pressure being taken three to five times daily in both the recumbent and the standing position. After two days in hospital a placebo capsule was given three times daily for two days to seven patients, after which they received methyldopa capsules on a similar schedule in daily doses ranging from 750 to 2,750 mg. for 2 to 10 days. When necessary the dose was increased every third day.Fourteen subjects were started immediately on methyltWe are grateful to Dr. K. C. Mezey, of Merck Sharpe and Dohme International, for supplying the aldomet used in this study.