Biological Sciences: Reduction of Catechol-O-methyl-transferase Activity by Chronic L-Dopa Therapy

Abstract

THE use of large doses of L-dopa, the immediate precursor of dopamine, in the symptomatic treatment of Parkinsonism has prompted investigation of the effects of this amino-acid on enzymes involved in catecholamine metabolism. It has been found that the activity of enzymes mediating the synthesis of catecholamines, such as tyrosine hydroxylase¹ and aromatic L-amino-acid decarboxylase (personal communication with W. Dairman and S. Udenfriend), diminishes during prolonged L-dopa administration. Conversely, monoamine oxidase, one of the enzymes involved in catecholamine degradation, has been found to increase in the tissues of animals given L-dopa² as well as in the serum of patients treated with this drug³. We now report a substantial decline in the activity of catechol-O-methyltransferase (COMT), another enzyme important in mediating catecholamine catabolism, in the red blood cells of Parkinsonian patients receiving chronic L-dopa treatment.