An evaluation of N,N-dipropargyl-2-phenylethylamine (DPGPEA) as a prodrug to increase brain levels of 2-phenylethylamine (PEA) was conducted in rats. A 0.1 mmol/kg (IP) dose of DPGPEA was administered and produced marked elevations of PEA levels in brain, liver and blood which were sustained for several hours. Ex vivo MAO inhibition data indicated DPGPEA to be an inhibitor of MAO-B, although the effect was much weaker than seen with tranylcypromine or pargyline. DPGPEA caused brain noradrenaline, dopamine and 3,4-dihydroxyphenylacetic acid levels to temporarily decrease significantly below controls. Concomitant increases in homovanillic acid and 5-hydroxyindole-3-acetic acid levels suggest that the PEA or N-propargylPEA formed and/or DPGPEA itself have significant effects on release and reuptake of neurotransmitters. DPGPEA was also shown to be metabolized to N-propargyl-PEA, another prodrug of PEA, in vivo.