[Iprindole: a functional link between serotonin and noradrenaline systems?].
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)
Ganry
H
H
Département de Pharmacologie et Gis Médicament, Faculté de Médecine, Nantes.
Bourin
M
M
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007488:Iprindole / Q000494:pharmacology*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000502:physiology; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011985:Receptors, Serotonin; D015016:Yohimbine; D012701:Serotonin; D007488:Iprindole; D001058:Apomorphine; D009638:Norepinephrine
Iprindole: lien fonctionnel entre systèmes sérotoninergique et noradrénergique?