Transamination is a Major Pathway of L-Dopa Metabolism following Peripheral Decarboxylase Inhibition

Abstract

WHEN L-3,4-dihydroxyphenylalanine (L-dopa) is administered to human subjects¹, the greater proportion is metabolised by decarboxylation, a small amount by O-methylation and traces only by transamination². It seems likely that the benefit resulting from L-dopa therapy in Parkinsonian patients derives largely from the generation of one of its metabolites, dopamine, by decarboxylation within the central nervous system³. Less than 5% of administered L-dopa becomes available for this purpose: most of the dose is decarboxylated peripherally⁴. There is good reason to believe that the dopamine so formed is unable to penetrate the blood-brain barrier to any great extent⁵, so that little of the original dose is available to contribute to the therapeutic response. By blocking peripheral decarboxylase, however, certain decarboxylase inhibitors^6,7, which are themselves unable to cross the blood-brain barrier to any significant extent⁸, bring about an accumulation in the plasma of administered L-dopa, thus providing a higher concentration gradient to enter the central nervous system and allowing lower oral doses of L-dopa to be employed therapeutically⁹.