Some biochemical and pharmacological actions of α-methylphenylalanine

Abstract

The catecholamine-depleting activity and certain pharmacological actions of l- α-methylphenylalanine, a tyrosine hydroxylase inhibitor, were compared in a number of species with those of the related α-methyl amino acids, l- α-methyl- p-tyrosine and dl- α-methyl- m-tyrosine. α-Methylphenylalanine was more active than α-methyl- p-tyrosine in depleting heart norepinephrine, but was less effective in reducing central amines; in addition, its duration of action in the heart was more prolonged. α-Methyl- m-tyrosine proved to be the most active compound on both brain and heart catecholamines. Metaraminol was found to be a metabolite of α-methylphenylalanine and was identified in the hearts, brains and adrenals of mice, rats and dogs. No overt signs of sedation were seen in dogs or squirrel monkeys given α-methylphenylalanine, although loss of avoidance responding could be demonstrated. This contrasted with results obtained with α-methyl- m-tyrosine, which produces stimulation and an increase in lever-pressing behavior. α-Methylphenylalanine, as found with α-methyl- p-tyrosine and α-methyl- m-tyrosine, reduced cardiac responses to the indirect sympathomimetic amines and to adrenergic nerve stimulation. It was concluded that the pattern of biochemical and pharmacologie events after α-methylphenylalanine falls between those because of α-methyl- p-tyrosine, a relatively pure tyrosine hydroxylase inhibitor, and α-methyl- m-tyrosine, whose effects are related predominantly to its rapid metabolism to metaraminol with a consequent release and depletion of catecholamines.