Quipazine: Its effects on rat brain 5-hydroxytryptamine metabolism, monoamine oxidase activity and behaviour

Abstract

Quipazine (2-(l-piperazinyl) quinoline maleate) administration (25 mg/kg) to rats produced behavioural changes, including hyperactivity, identical to those seen following tranylcypromine and l-tryptophan. This suggests that quipazine is a 5-hydroxytryptamine agonist and this view is strengthened by the observation that when quipazine was given to rats pretreated with p-chlorophenylalanine. the hyperactivity was enhanced. α-Methyl- p-tyrosine pretreatment diminished the behavioural responses and previous experiments have suggested that dopamine is involved in the behavioural responses to increased 5-hydroxytryptamine receptor stimulation. Quipazine did not alter the concentration of brain tryptophan but caused a small rise of brain 5-hydroxytryptamine. Oxidation of 5-hydroxytryptamine and dopamine by monoamine oxidase (MAO) was partially inhibited during this period. Tryptamine oxidation, however, was unaffected. In vitro studies demonstrated that quipazine inhibited MAO activity reversibly and competitively. Dopamine and 5-hydroxytryptamine oxidation were more readily inhibited than tryptamine and kynuramine, which suggests that quipazine is predominantly a type A MAO inhibitor. Quipazine-induced hyperactivity was enhanced by administration of deprenil, a type B MAO inhibitor, but not by the type A MAO inhibitor clorgyline. Quipazine plus deprenil inhibited oxidation of both 5-hydroxytryptamine (a type A substrate) and phenylethylamine (a type B substrate). Since dopamine is metabolised by both forms of the enzyme, one interpretation of these results is that when MAO activity is inhibited in dopaminergic neurones the hyperactivity following 5-hydroxytryptamine receptor stimulation is enhanced. We conclude that quipazine is a 5-hydroxytryptamine agonist with weak reversible MAO inhibitory action.