Deprenyl alters behavior and caudate dopamine through an amphetamine-like action

doi:10.1016/0091-3057(92)90484-W

Pharmacology Biochemistry and Behavior

Volume 43, Issue 4, December 1992, Pages 1075-1080

https://doi.org/10.1016/0091-3057(92)90484-W Get rights and content

Abstract

In vivo microdialysis was used to concurrently measure the behavioral and caudate dopamine (DA) responses to the alleged irreversible type B monoamine oxidase inhibitor deprenyl. The effects were contrasted to those of the type A monoamine oxidase inhibitor, clorgyline. Consistent with its effects as an irreversible monoamine oxidase inhibitor, clorgyline produced an increase in DA concentration that remained elevated for at least 6 h. In contrast, the deprenyl-induced elevation in DA concentration occurred more rapidly, achieved a higher peak response, and then returned to baseline within 2 h following drug administration. The two drugs also produced distinctive changes in DA metabolite levels. Whereas the pattern of clorgyline-induced effects were consistent with irreversible monoamine oxidase inhibition, deprenyl produced an amphetamine-like response profile. Further, deprenyl but not clorgyline significantly increased locomotor activity. These results suggest that deprenyl does not augment caudate DA levels through monoamine oxidase inhibition. Rather, the pattern of its effects on caudate DA dynamics and behavior supports previous evidence that deprenyl produces its effects through its metabolism to amphetamine-like substances.

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Deprenyl alters behavior and caudate dopamine through an amphetamine-like action

Abstract

Prog. Neurobiol.

Biochem. Pharmacol.

Brain Res.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Pharmacol. Biochem. Behav.

Biochem. Pharmacol.

The histochemical discrimination between type A and B MAO in rat brain

Neurosci. Lett.

Brain microdialysis

J. Neurochem.

The potentiation of the anti-akinetic effect after l-dopa treatment by an inhibitor of MAO-B, deprenyl

J. Neural Trans.

Effects of selective monoamine oxidase inhibitors on the in vivo release and metabolism of dopamine in the rat striatum

J. Neurochem.

Type A monoamine oxidase catalyzes the intraneuronal deamination of dopamine within nigrostriatal mesolimbic, tuberoinfundibular and tuberohypophyseal neurons in the rat

J. Neural Trans.

The presence of the type A form of monoamine oxidase within nigrostriatal dopamine-containing neurons

J. Pharmacol. Exp. Ther.

Deprenyl in Parkinson disease

Neurology

Deprenyl (Selegiline), a selective MAO-B inhibitor with active metabolites: Effects on locomotor activity, dopaminergic neurotransmission and firing rate of nigral dopamine neurons

J. Pharmacol. Exp. Ther.

Evidence for dopamine deamination by both type A and type B monoamine oxidase in rat brain in vivo and for the degree of inhibition of enzyme necessary for increased functional activity of dopamine and 5-hydroxytryptamine

Br. J. Pharmacol.

Release of endogenous dopamine from rat isolated stratum: Effect of clorgyline and (−)-deprenyl

Br. J. Pharmacol.

Pharmacokinetics and metabolism of Selegiline

Acta Neurol. Scand.

Striatal membrane-bound and soluble catechol-O-methyl-transferase after selective neuronal lesions in the rat

J. Neural Trans.

Metabolism of (−)-deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: A biochemical assessment

Neurology