The monoamine oxidase B inhibitor deprenyl potentiates phenylethylamine behaviour in rats without inhibition of catecholamine metabolite formation.
The drug l-deprenyl has been reported to have antidepressant properties, and in the present study three possible mechanisms of action were investigated in animal experiments. l-Deprenyl, which is a type B monoamine oxidase (MAO) inhibitor, was compared to clorgyline, an MAO A inhibitor with regard to its inhibitory effect on the formation of three major catecholamine metabolites, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MOPEG) in the rat brain in vivo. Apart from a difference in dose levels the two drugs showed no difference in the dose--response pattern of all three metabolites. Clorgyline inhibited the formation of HVA, DOPAC and MOPEG with an ED50 of about 0.2 mg/kg s.c. and l-deprenyldopamine and noradrenaline are formed by the same type of monoamine oxidase(s), probably type A, in the rat brain in vivo. Antidepressant properties of l-deprenyl therefore seem to be independent of catecholamine deamination. l-Deprenyl but not clorgyline (2 or 8 mg/kg s.c.) potentiated the stereotyped sniffing behaviour induced by beta-phenylethylamine, a specific substrate for type B monoamine oxidase. This result is discussed in relation to a new hypothesis of phenylethylamine and dopamine involvement in depression. l-Deprenyl was 10,000 times less potent than DMI as inhibitor of noradrenaline uptake in crude synaptosomes from the occipital cortex of rat brain. Inhibition of noradrenaline uptake was therefore excluded as a possible mechanism for the antidepressant action of l-deprenyl.
D000818:Animals; D001519:Behavior / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002395:Catecholamines / Q000378:metabolism*; D003010:Clorgyline / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010084:Oxidation-Reduction; D010627:Phenethylamines / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects*; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D002395:Catecholamines; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D011437:Propylamines; D003010:Clorgyline; D009638:Norepinephrine