The Effects of Pargyline, Clorgyline, Deprenyl and their Metabolites on Rat Peripheral and Central Biogenic Amines: A Comparison between Changes in Urine Excretion and Brain Concentrations

Abstract

The chronic effects of pargyline, clorgyline, deprenyl and their metabolites on central and peripheral biogenic amines were evaluated in rats. The amines studies are phenylethylamine (PEA), p-tyramine (Ty), norepinephrine (NE) and tryptamine (TP). All analyses were carried out by mass fragmentography. Pargyline gave rise to three dealkylated products: benzylamine, N-methylbenzylamine and N-propargylbenzylamine (NPB). Of these three metabolites only NPB had in vivo monoamine oxidase (MAO) inhibitory properties. NPB like pargyline markedly elevated urine and brain PEA while only pargyline reduced peripheral and brain 5HT metabolism, suggesting that the metabolism of pargyline to NPB may be largely responsible for MAO type B inhibition. Pargyline, clorgyline, deprenyl, and NPB reduced NE and DA metabolism as reflected upon urine and brain concentrations of the metabolites. These effects remained evident 24 hours after termination of treatment. In contrast to their expected effects on urine and brain PEA and Ty, none of these above four drugs reduced 5HT and TP metabolism as would be expected from their in vitro properties. Furthermore, the relatively mild reductions in 5-hydroxyindole acetic acid (5HIAA) observed after pargyline and clorgyline disappeared 24 hours after drug treatment signifying paradoxically a transient and short lived inhibition of peripheral 5HT metabolism. The effects of D-and L-amphetamine on biogenic amines were also studied. These amines are metabolites of deprenyl in vivo. Both isomers produced peripheral and central changes that are similar, thus adding support to the notion that the in vivo etfects of deprenyl on PEA is at least partially related to its metabolism to amphetamine and methamphetamine. Further, in view of the similarities in their effects on the amines studies here, it is unlikely that the behavioral differences between D- and L- amphetamine are directly mediated via changes in perhipheral or central catecholamines, PEA or p-Ty.