These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Coincidence of blockade of synaptosomal 5-hydroxytryptamine uptake and decrease in tryptophan hydroxylase activity: effects of fenfluramine.
    Author: Knapp S, Mandell AJ.
    Journal: J Pharmacol Exp Ther; 1976 Jul; 198(1):123-32. PubMed ID: 933002.
    Abstract:
    A single injection of fenfluramine hydrochloride resulted in a short-term increase in striate synaptosomal conversion of tryptophan to serotonin (5-HT) in rat brain. In contrast, D- and L-amphetamine sulfate resulted in a short-term decrease of this index of 5-HT biosynthesis. None of the amphetamines studied altered the kinetics of synaptosomal uptake of L-[3-14C]-tryptophan measured in the same striate preparation. Within 4 hours after fenfluramine administration, 3H-5-HT uptake into synaptosomes was markedly decreased; it returned to control levels in 10 to 14 days. Intrasynaptosomal tryptophan hydroxylase activity dropped markedly within 4 hours of drug administration and remained depressed for 10 to 14 days, its return to control levels coinciding with that of 3H-5-HT uptake. Only 5-HT cell body enzyme prepared from the lateral midbrain (B9) demonstrated a reduction in activity comparable to that seen in the synaptosomes; very small decreases occurred in cell body enzyme prepared from whole midbrain (B7, B8, B9) or medial midbrain (B7, B8). Lateral midbrain tryptophan hydroxylase activity returned to control levels by 8 days. In vitro, fenfluramine (100 muM) affected none of these indices of central 5-HT synthesis except 3H-5-HT uptake, which it reduced, and synaptosomal 3H-5-HT release, which it facilitated. The effects of fenfluramine on 5-HT biosynthesis persisted longer than those of D-amphetamine, which lasted less than 24 hours. However, the fenfluramine effects were much shorter than those reported for p-chloroamphetamine, which persist for up to 3 months. These three amphetamines apparently affect the lateral midbrain raphe nuclei selectively.
    [Abstract] [Full Text] [Related] [New Search]