[Iprindole: a functional link between serotonin and noradrenaline systems?].

H Ganry; M Bourin

PubMed · 8174513

[Iprindole: a functional link between serotonin and noradrenaline systems?].

Abstract

Iprindole is an active antidepressant in clinical practice but its mechanism of action has never been clearly defined. Serotoninergic regulation of noradrenergic neurons of locus coeruleus depends on 5-HT2 receptors. This regulatory action of the 5-HT system appears to facilitate the down-regulation of beta receptors. In behavioural tests involving the noradrenergic system, the role of iprindole, administered in subactive doses, was evaluated in the presence of subactive doses of fluvoxamine, a serotonin uptake inhibitor. Yohimbine is an alpha2 antagonist, inducing a dose-dependent toxicity. This test allows a rapid and selective screening of antidepressants with direct and indirect beta-agonist properties. Administration of iprindole displayed a toxicity of fluvoxamine in the presence of yohimbine. A 5-day pre-treatment of iprindole antagonized this potentiation unmasked after acute administration of iprindole. The down-regulation of beta receptors induced by a chronic treatment by iprindole could prevent the adrenergic expression of yohimbine's toxicity. But the down-regulation of 5-HT2 receptors also obtained with chronic treatment by iprindole, can explain this antagonism preventing fluvoxamine's action. Hypothermia induced by a high dose of apomorphine, depends on an activation of the noradrenergic system. During the interaction with fluvoxamine, iprindole unmasked an antagonism of this hypothermia due to apomorphine. The activity of a subactive dose of salbutamol, a direct beta-agonist, was evaluated in the presence of fluvoxamine on hypothermia induced by a high dose of apomorphine. The aim of this interaction was to define the beta-adrenergic property of iprindole more precisely.(ABSTRACT TRUNCATED AT 250 WORDS)

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Animals Apomorphine Arousal Body Temperature Regulation Brain Dose-Response Relationship, Drug Iprindole Lethal Dose 50 Male Mice Norepinephrine Receptors, Adrenergic Receptors, Serotonin Serotonin Yohimbine English Abstract Journal Article

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H Ganry, M Bourin. [Iprindole: a functional link between serotonin and noradrenaline systems?].. https://pubmed.ncbi.nlm.nih.gov/8174513/

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