d-Fenfluramine and d-norfenfluramine hypophagias do not require increased hypothalamic 5-hydroxytryptamine release.
d-Fenfluramine (2.5 mg/kg i.p.) caused marked hypophagia in food-deprived rats and significantly increased medial hypothalamic extracellular 5-hydroxytryptamine (5-HT) as indicated by in vivo microdialysis. When the drug was given after the 5-HT synthesis inhibitor p-chlorophenylalanine (150 mg/kg per day x 3) the hypophagic response was unimpaired but dialysate 5-HT concentration no longer rose. The d-fenfluramine metabolite d-norfenfluramine (1.5 mg/kg i.p.) caused slightly greater hypophagia than the parent drug and completely blocked feeding in animals pretreated with p-chlorophenylalanine, but dialysate 5-HT was increased in neither circumstance. The results provide evidence against mediation of the hypophagic effects of d-fenfluramine and d-norfenfluramine by increased availability of 5-HT to receptors.
Oluyomi
A O
AO
Department of Neurochemistry, Institute of Neurology, London, UK.
Gibson
E L
EL
Barnfield
A M
AM
Curzon
G
G
D000818:Animals; D004435:Eating; D001068:Feeding and Eating Disorders / Q000139:chemically induced* / Q000378:metabolism; D010134:Fenclonine / Q000494:pharmacology; D005277:Fenfluramine / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009642:Norfenfluramine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
D011985:Receptors, Serotonin; D009642:Norfenfluramine; D005277:Fenfluramine; D012701:Serotonin; D010134:Fenclonine