d-fenfluramine, but not d-norfenfluramine, uses calcium to increase extracellular serotonin.
Microdialysis in the hippocampus of freely moving rats was used to assess extracellular serotonin (5-HT) in response to local infusion of d-fenfluramine and its metabolite d-norfenfluramine with and without local calcium depletion. Verapamil (1 mM) in calcium-free Ringer infused via the microdialysis probe increased extracellular 5-HT and prevented the full increase in extracellular 5-HT normally caused by 1 mM d-fenfluramine. The results suggest d-fenfluramine might act in part as a calcium channel agonist favoring a calcium influx that in turn would trigger the exocytotic process in 5-HT terminals. d-norfenfluramine, on the other hand, was capable of releasing 5-HT, in vivo, in spite of depleted Ca levels.
Puig de Parada
M
M
Princeton University, Department of Psychology, NJ, USA.
Parada
M A
MA
Pothos
E
E
Hoebel
B G
BG
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005277:Fenfluramine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009642:Norfenfluramine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*; D014700:Verapamil / Q000494:pharmacology
D009642:Norfenfluramine; D005277:Fenfluramine; D012701:Serotonin; D014700:Verapamil; D002118:Calcium