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Suppression of behavioral activity by norfenfluramine and related drugs in rats is not mediated by serotonin release.
Psychopharmacology (Berl). 1993; 111(2):169-78.P

Abstract

Fenfluramine, a phenalkylamine with serotonin (5-HT) releasing properties, decreases motor activity in rats. The following studies assessed the contribution of 5-HT release to the behavioral effects of fenfluramine and norfenfluramine using a behavioral pattern monitor that simultaneously assesses locomotor and investigatory behavior. First, both fenfluramine and its active metabolite d-norfenfluramine dose-dependently reduced locomotor and investigatory activity. The norfenfluramine-induced reduction in activity was not antagonized by pretreatment with the 5-HT uptake inhibitor fluoxetine or the 5-HT synthesis inhibitor p-chlorophenylalanine, drugs that reduce drug-induced 5-HT release. Second, the d- and l-enantiomers of norfenfluramine were nearly equipotent at reducing behavioral activity, although d-norfenfluramine is more potent as a 5-HT releasing agent. Third, p-chloroamphetamine, a drug that shares the 5-HT releasing properties of fenfluramine produced locomotor hyperactivity in the same paradigm. Previous studies indicate that other 5-HT releasing phenalkylamines have behavioral effects resembling those of p-chloroamphetamine rather than those of fenfluramine. Finally, a structurally related drug, 4-methoxy-5-methyl-aminoindan (MMAI), produced dose-dependent reductions in behavioral activity that are similar to the effects of fenfluramine. The behavioral effects of MMAI were not antagonized by fluoxetine or by the 5-HT receptor antagonist methiothepin. These data suggest that the decrease in activity induced by fenfluramine, norfenfluramine and the related drug MMAI is not related to 5-HT release.

Authors+Show Affiliations

Department of Psychiatry, UCSD School of Medicine, La Jolla 92093-0804.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7870948

Citation

Callaway, C W., et al. "Suppression of Behavioral Activity By Norfenfluramine and Related Drugs in Rats Is Not Mediated By Serotonin Release." Psychopharmacology, vol. 111, no. 2, 1993, pp. 169-78.
Callaway CW, Wing LL, Nichols DE, et al. Suppression of behavioral activity by norfenfluramine and related drugs in rats is not mediated by serotonin release. Psychopharmacology (Berl). 1993;111(2):169-78.
Callaway, C. W., Wing, L. L., Nichols, D. E., & Geyer, M. A. (1993). Suppression of behavioral activity by norfenfluramine and related drugs in rats is not mediated by serotonin release. Psychopharmacology, 111(2), 169-78.
Callaway CW, et al. Suppression of Behavioral Activity By Norfenfluramine and Related Drugs in Rats Is Not Mediated By Serotonin Release. Psychopharmacology (Berl). 1993;111(2):169-78. PubMed PMID: 7870948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of behavioral activity by norfenfluramine and related drugs in rats is not mediated by serotonin release. AU - Callaway,C W, AU - Wing,L L, AU - Nichols,D E, AU - Geyer,M A, PY - 1993/1/1/pubmed PY - 1993/1/1/medline PY - 1993/1/1/entrez SP - 169 EP - 78 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 111 IS - 2 N2 - Fenfluramine, a phenalkylamine with serotonin (5-HT) releasing properties, decreases motor activity in rats. The following studies assessed the contribution of 5-HT release to the behavioral effects of fenfluramine and norfenfluramine using a behavioral pattern monitor that simultaneously assesses locomotor and investigatory behavior. First, both fenfluramine and its active metabolite d-norfenfluramine dose-dependently reduced locomotor and investigatory activity. The norfenfluramine-induced reduction in activity was not antagonized by pretreatment with the 5-HT uptake inhibitor fluoxetine or the 5-HT synthesis inhibitor p-chlorophenylalanine, drugs that reduce drug-induced 5-HT release. Second, the d- and l-enantiomers of norfenfluramine were nearly equipotent at reducing behavioral activity, although d-norfenfluramine is more potent as a 5-HT releasing agent. Third, p-chloroamphetamine, a drug that shares the 5-HT releasing properties of fenfluramine produced locomotor hyperactivity in the same paradigm. Previous studies indicate that other 5-HT releasing phenalkylamines have behavioral effects resembling those of p-chloroamphetamine rather than those of fenfluramine. Finally, a structurally related drug, 4-methoxy-5-methyl-aminoindan (MMAI), produced dose-dependent reductions in behavioral activity that are similar to the effects of fenfluramine. The behavioral effects of MMAI were not antagonized by fluoxetine or by the 5-HT receptor antagonist methiothepin. These data suggest that the decrease in activity induced by fenfluramine, norfenfluramine and the related drug MMAI is not related to 5-HT release. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/7870948/Suppression_of_behavioral_activity_by_norfenfluramine_and_related_drugs_in_rats_is_not_mediated_by_serotonin_release_ DB - PRIME DP - Unbound Medicine ER -