The effects of chronic treatment with the 5-hydroxytryptamine uptake blocker zimelidine on central 5-hydroxytryptamine mechanisms. Evidence for the induction of a low affinity binding site for 5-hydroxytryptamine.
Male rats were treated with saline or the 5-hydroxytryptamine (5-HT) uptake inhibitor zimelidine (10 mumol/kg postoperatively) twice daily for a period of 14 days. The effects of this treatment on [5-3H]HT binding in the cerebral cortex and hypothalamus and on 5-HT synthesis were examined. Long-term treatment with zimelidine induced a low affinity site for 5-HT (Kd approximately 20 nM) in both areas and a reduced number of high affinity binding sites in the hypothalamus. Long-term zimelidine treatment did not attenuate the feed-back mediated inhibition of 5-HT synthesis. These findings suggest that chronic zimelidine treatment could result in a reduced activity at postsynaptic 5-HT receptor sites.
D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000499:Allylamine