Progress report on the anorectic effects of dexfenfluramine, fluoxetine and sertraline.
This progress report on the anorectic effect of serotoninergic indirect antagonists compares the action of D-fenfluramine, fluoxetine and sertraline and their N-dealkylated metabolites. Brain levels of drugs and their metabolites were measured after equi-active anorectic doses. Fluoxetine and sertraline inhibit 5-HT uptake in vitro with a potency which is at least one order of magnitude higher than for D-fenfluramine while all three drugs release 5-HT from synaptosomes and the active concentrations are closer to the brain concentrations reached after anorectic doses. However, a number of differences have been observed between D-fenfluramine and fluoxetine regarding the mechanisms of 5-HT release. Furthermore fluoxetine affected storage of 5-HT in vesicles much more than D-fenfluramine did. The anorectic effect induced by fluoxetine was not antagonized by antiserotoninergic drugs. No evidence of an involvement of CCK in the anorectic effect of D-fenfluramine was found when food intake was determined in rats previously submitted to food deprivation.
Garattini
S
S
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Bizzi
A
A
Caccia
S
S
Mennini
T
T
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001067:Appetite Depressants / Q000493:pharmacokinetics / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005277:Fenfluramine / Q000493:pharmacokinetics / Q000494:pharmacology*; D005473:Fluoxetine / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D020280:Sertraline
D001067:Appetite Depressants; D012702:Serotonin Antagonists; D005473:Fluoxetine; D005277:Fenfluramine; D012701:Serotonin; D015057:1-Naphthylamine; D020280:Sertraline