Is receptor activation involved in the mechanism by which (+)-fenfluramine and (+)-norfenfluramine deplete 5-hydroxytryptamine in the rat brain?
1 The effects of (+)-fenfluramine, (+)-norfenfluramine and reserpine on the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brainstem and telencephalon were studied in rats treated with methergoline, a 5-HT antagonist. 2 Methergoline significantly reduced the effect of (+)-norfenfluramine (5 mg/kg) on 5-HT levels in telencephalon and brainstem but did not modify the effect of (+)-norfenfluramine (2.5 mg/kg). 3 Neither the effect of (+)-fenfluramine on 5-HT levels nor the decrease of 5-HT metabolism caused by (+)-fenfluramine and (+)-norfenfluramine was significantly modified by methergoline treatment. 4 Methergoline potentiated the effects of reserpine on brain indoles. The effects was particularly evident on 5-HIAA levels in the brainstem, although significant effects were found on 5-HT in the brainstem and 5-HIAA in the telencephalon depending on the dose reserpine used. 5 The results show that postsynaptic receptor activation may partially contribute to the depletion of brain 5-HT caused by (+)-norfenfluramine in the rat. This mechanism does not seem to play a significant role in the effect of (+)-fenfluramine.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D005260:Female; D005277:Fenfluramine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008711:Metergoline / Q000494:pharmacology; D009642:Norfenfluramine / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*
D011985:Receptors, Serotonin; D008711:Metergoline; D009642:Norfenfluramine; D005277:Fenfluramine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D012110:Reserpine