In vivo intraneuronal MAO inhibition in rat brain SKF 64139, comparison to other potent PNMT inhibitors.

SKF 64139, a potent inhibitor of adrenal and brain phenylethanolamine-N-methyltransferase (PNMT), was found to have effects on catecholamines, serotonin and their metabolites in rat brain which suggest it may act as a potent inhibitor of monoamine oxidase (MAO) 'in vivo' after acute administration. Evidence of this was obtained by observing the concurrent elevation of serotonin and depletion of its major metabolite 5-hydroxyindoleacetic acid (5-HIAA), as well as depletion of the dopamine metabolites homovanillic acid and 3,4-dihydroxyphenyl-acetic acid (DOPAC) following acute administration. Additional evidence was obtained by antagonism of the increase in acid metabolites and depletion of amines following treatment with reserpine. Using the depletion of brain DOPAC as an index of MAO activity, an ED50 of 3-4 mg/kg was found for SKF 64139 as an "in vivo' MAO inhibitor.