title: From fenfluramine racemate to d-fenfluramine. Specificity and potency of the effects on the serotoninergic system and food intake.
abstract: Experiments using the binding of various ligands for monoamines to rat brain membranes and synaptosomal preparations for studying monoamine uptake and release have shown that d-fenfluramine is more potent than the l isomer in inhibiting 5-HT uptake, whereas d-norfenfluramine preferentially releases 5-HT from a reserpine-insensitive compartment. Studies on brain monoamine metabolism in intact animals have shown that the d and l isomers of fenfluramine at relatively low doses have a specific action on brain 5-HT and catecholamines, respectively. Based on the different ability of metergoline and ritanserin to displace 5-HT2 binding to rat brain membranes and to antagonize d-fenfluramine's anorexia, evidence has been provided that d-fenfluramine preferentially uses 5-HT1 sites in the rat brain to cause anorexia in this animal species. Finally, characteristics, regional distribution, and pharmacological characterization of a high-affinity [3H]d-fenfluramine binding to rat brain membranes have been described. This binding appears to be different from 5-HT uptake sites ([3H]imipramine binding) and 5-HT receptors and is not regionally related to the endogenous levels of 5-HT in the rat brain. It is, however, preferentially displaced by some agents using 5-HT to cause anorexia in rats, raising the possibility that it is somewhat related to 5-HT mechanisms involved in feeding control.
mesh_terms: D000588:Amines / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D003913:Dextroamphetamine / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007536:Isomerism; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D000588:Amines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D005277:Fenfluramine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003913:Dextroamphetamine