Clinical and Chemical Studies with α -Methyl-Dopa in Patients with Hypertension

Abstract

A series of observations in 52 hypertensive patients is presented indicating that α-methyl-dopa is an effective antihypertensive agent. The antihypertensive properties of the agent were discovered in the course of biochemical studies with the racemic compound the form used in initial therapeutic trials. Studies on metabolism of dl-α-methyl-dopa indicate incomplete intestinal absorption and rapid excretion in the urine as unchanged drug and as α-methyl-dopamine. The former finding does not seem to be a significant deterrent to its use orally. Comparisons of the d and l isomers of α-methyl-dopa in hypertensive patients showed that all the chemical and pharmacologic effects reside in the l-isomer (Aldomet). Thus, recent studies have been performed with Aldomet exclusively. From observations to date the impression has been gained that Aldomet has several advantages over other antihypertensive agents; these include effectiveness against all degrees of hypertension, frequent lowering of recumbent as well as standing blood pressure, smoothness of effect, and tranquilizing effects. Questions of toxicity and tolerance are not yet completely answered. Sympathetic blockade at a central or peripheral site is the probable basis of the drug's action. This effect may be unrelated to the biochemical property of inhibiting the decarboxylation of aromatic l-amino acids and is possibly due to depletion of tissue stores of norepinephrine by a mechanism not yet fully defined.