Combined clinical and metabolic study of the effects of alpha-methyldopa on hypertensive patients.

ALPHA-METHYLDOPA (a-methyl-3,4-diIA hydroxy-L-phenylalanine [Aldomet]) is a useful antihypertensive agent with sedative and aromatic L-amino decarboxylase-inhibiting properties.'-7 It has several advantages over other potent antihypertensive drugs in current use. Reduction in blood pressure is achieved gradually and occurs in the lying as well as in the standing position. The lack of marked postural or exertional hypotension makes a-methyldopa particularly suitable for patients with coronary or cerebral artery disease, in whom sudden reduction in blood pressure may be disastrous. Symptoms of sympathetic blockade are uncommon, and renal vascular resistance is reduced,8 making it a potentially useful drug in the management of hypertension in patients with renal failure. On the other hand, in certain patients, rapid development of tolerance to the hypotensive effects of a-methyldopa has been noted,3 9-13 and in other patients little or no hypotensive effect is achieved. The mechanisms involved are unknown. The present clinical and metabolic study was undertaken to investigate the correlation between the metabolism of a-methyldopa and clinical response to the drug, and particularly to ascertain whether the development of tolerance could be related to changes