Pharmacokinetic and neurochemical studies on N-propargyl-2-phenylethylamine, a prodrug of 2-phenylethylamine.

Pharmacokinetic and neurochemical properties of N-propargyl-2-phenylethylamine, a known MAO inhibitor and a potential prodrug of the bioactive trace amine, 2-phenylethylamine, were studied in rats. Intraperitoneal (i.p.) administration of N-propargyl-2-phenylethylamine produced marked elevations in 2-phenylethylamine levels in rat brain, blood and liver; these levels remained significantly above controls for more than 4 h. Neurochemical studies showed the drug to be a preferential MAO-B inhibitor at a dose of 0.1 mmol/kg (i.p.). This selectivity was much more pronounced in liver than in brain. N-Propargyl-2-phenylethylamine produced a significant decrease in whole brain concentrations of noradrenaline, dopamine and DOPAC, but they returned to control values by 3 h after drug administration. Concentrations of 5-HT were unaffected, while 5-HIAA and HVA concentrations increased significantly above controls. Results indicate that N-propargyl-2-phenylethylamine is a prodrug of 2-phenylethylamine and a potentially useful pharmacological tool with which to study the functional role of 2-phenylethylamine in the mammalian central nervous system.