Effect of decarboxylase inhibitors on brain p-tyrosine levels

A number of inhibitors of L-aromatic amino acid decarboxylase (AAD) and monoamine oxidase (MAO) were tested to determine whether they also inhibited tyrosine aminotransferase (TAT). The AAD inhibitors carbidopa, NSD-1015, NSD-1034 and Ro4-5127 inhibited liver TAT. Carbidopa inhibited brain AAD and liver TAT equally well. In contrast, other AAD inhibitors (Ro4-4602 and alpha-monofluoromethyldopa) did not inhibit TAT. Phenelzine, an MAO inhibitor, inhibited liver TAT, but other MAO inhibitors (tranylcypromine and isocarboxazid) did not. Systemic administration of those drugs that were found to be inhibitors of TAT in vitro caused significant increases in rat brain p-tyrosine levels.