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Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors.
Neuropharmacology. 2001 Aug; 41(2):200-9.N

Abstract

The present series of studies is the first to investigate the pharmacological mechanisms underlying d-fenfluramine- and d-norfenfluramine-induced hypophagia in the rat using highly selective serotonin 5-HT2 receptor antagonists. Administration of d-fenfluramine, and its major metabolite d-norfenfluramine, suppresses food intake in animals. Both compounds stimulate the release of serotonin and are potent inhibitors of the re-uptake of 5-HT into nerve terminals. In addition, d-norfenfluramine also acts as a direct 5-HT(2B/2C) receptor agonist. Pre-treatment with the selective 5-HT2C receptor antagonist, SB-242084 (0.3-3 mg/kg), dose-dependently inhibited both d-fenfluramine- (3 mg/kg) and d-norfenfluramine-induced (2 mg/kg) hypophagia. In contrast, the hypophagic effect of d-fenfluramine and d-norfenfluramine was unaffected by prior treatment with the highly selective 5-HT2B receptor antagonists, SB-215505 (0.3-3 mg/kg) and RS-127445 (1-3 mg/kg) or the 5-HT2A receptor antagonists MDL 100,907 (0.003-0.03 mg/kg) and ketanserin (0.2, 0.5 mg/kg). In addition, the 5-HT1A receptor antagonist WAY-100635 (0.3, 1 mg/kg) and the 5-HT1B receptor antagonists GR-127935 (1, 2 mg/kg) and SB-224289 (2-10 mg/kg) did not affect d-fenfluramine-induced hypophagia. These data provide unequivocal evidence for an important role of the 5-HT2C receptor in the mediation of d-fenfluramine and d-norfenfluramine-induced hypophagia in the rat and do not support the involvement of 5-HT1A/1B/2A/2B receptors.

Authors+Show Affiliations

Vernalis Research Limited, Oakdene Court, 613 Reading Road, Winnersh RG41 5UA, UK. s.vickers@vernalis.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11489456

Citation

Vickers, S P., et al. "Evidence That Hypophagia Induced By D-fenfluramine and D-norfenfluramine in the Rat Is Mediated By 5-HT2C Receptors." Neuropharmacology, vol. 41, no. 2, 2001, pp. 200-9.
Vickers SP, Dourish CT, Kennett GA. Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. Neuropharmacology. 2001;41(2):200-9.
Vickers, S. P., Dourish, C. T., & Kennett, G. A. (2001). Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. Neuropharmacology, 41(2), 200-9.
Vickers SP, Dourish CT, Kennett GA. Evidence That Hypophagia Induced By D-fenfluramine and D-norfenfluramine in the Rat Is Mediated By 5-HT2C Receptors. Neuropharmacology. 2001;41(2):200-9. PubMed PMID: 11489456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. AU - Vickers,S P, AU - Dourish,C T, AU - Kennett,G A, PY - 2001/8/8/pubmed PY - 2001/10/12/medline PY - 2001/8/8/entrez SP - 200 EP - 9 JF - Neuropharmacology JO - Neuropharmacology VL - 41 IS - 2 N2 - The present series of studies is the first to investigate the pharmacological mechanisms underlying d-fenfluramine- and d-norfenfluramine-induced hypophagia in the rat using highly selective serotonin 5-HT2 receptor antagonists. Administration of d-fenfluramine, and its major metabolite d-norfenfluramine, suppresses food intake in animals. Both compounds stimulate the release of serotonin and are potent inhibitors of the re-uptake of 5-HT into nerve terminals. In addition, d-norfenfluramine also acts as a direct 5-HT(2B/2C) receptor agonist. Pre-treatment with the selective 5-HT2C receptor antagonist, SB-242084 (0.3-3 mg/kg), dose-dependently inhibited both d-fenfluramine- (3 mg/kg) and d-norfenfluramine-induced (2 mg/kg) hypophagia. In contrast, the hypophagic effect of d-fenfluramine and d-norfenfluramine was unaffected by prior treatment with the highly selective 5-HT2B receptor antagonists, SB-215505 (0.3-3 mg/kg) and RS-127445 (1-3 mg/kg) or the 5-HT2A receptor antagonists MDL 100,907 (0.003-0.03 mg/kg) and ketanserin (0.2, 0.5 mg/kg). In addition, the 5-HT1A receptor antagonist WAY-100635 (0.3, 1 mg/kg) and the 5-HT1B receptor antagonists GR-127935 (1, 2 mg/kg) and SB-224289 (2-10 mg/kg) did not affect d-fenfluramine-induced hypophagia. These data provide unequivocal evidence for an important role of the 5-HT2C receptor in the mediation of d-fenfluramine and d-norfenfluramine-induced hypophagia in the rat and do not support the involvement of 5-HT1A/1B/2A/2B receptors. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/11489456/Evidence_that_hypophagia_induced_by_d_fenfluramine_and_d_norfenfluramine_in_the_rat_is_mediated_by_5_HT2C_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028390801000636 DB - PRIME DP - Unbound Medicine ER -