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Anorectic effect and brain concentrations of D-fenfluramine in the marmoset: relationship to the in vivo and in vitro effects on serotonergic mechanisms.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Mar; 347(3):306-12.NS

Abstract

The present study investigated the anorectic activity of d-fenfluramine (d-F) and the relationship with brain levels of unchanged drug and its metabolite d-norfenfluramine (d-NF) in marmosets, relating them to neurochemical effects on the serotoninergic system. d-F and d-NF were equally active in reducing food intake (ED50 about 3 mg/kg, p.o.). However, the brain concentrations of the metabolite required to reduce food intake after synthetic d-NF were more than twice those after d-F, indicating that d-NF contributes to but does not completely explain the anorectic effect of d-F. At this dose d-F did not appreciably modify the serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) contents of the brain regions examined, except for a slight enhancement of 5-HIAA in hippocampus. In vitro in brain cortical synaptosomes d-F inhibited [3H]5-HT uptake more potently than d-NF, as in other species. d-F and d-NF showed similar potency in stimulating [3H]5-HT release, in a Ca++ dependent manner. The tritium released by d-F and d-NF appeared to be mainly unmetabolized [3H]5-HT. Like in other species the marmoset too has saturable and specific [3H]d-F binding sites, for which d-NF has lower affinity. d-F and d-NF have low affinities for 5-HT receptor subtypes, except that d-NF has appreciable affinity for 5-HT1C and 5-HT1D receptors. Unlike in rodents but similarly to primates in the striatum the pharmacology of 5-HT receptors seems to correspond to the 5-HT1D subtype.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8479546

Citation

Caccia, S, et al. "Anorectic Effect and Brain Concentrations of D-fenfluramine in the Marmoset: Relationship to the in Vivo and in Vitro Effects On Serotonergic Mechanisms." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 347, no. 3, 1993, pp. 306-12.
Caccia S, Anelli M, Fracasso C, et al. Anorectic effect and brain concentrations of D-fenfluramine in the marmoset: relationship to the in vivo and in vitro effects on serotonergic mechanisms. Naunyn Schmiedebergs Arch Pharmacol. 1993;347(3):306-12.
Caccia, S., Anelli, M., Fracasso, C., Frittoli, E., Giorcelli, P., Gobbi, M., Taddei, C., Garattini, S., & Mennini, T. (1993). Anorectic effect and brain concentrations of D-fenfluramine in the marmoset: relationship to the in vivo and in vitro effects on serotonergic mechanisms. Naunyn-Schmiedeberg's Archives of Pharmacology, 347(3), 306-12.
Caccia S, et al. Anorectic Effect and Brain Concentrations of D-fenfluramine in the Marmoset: Relationship to the in Vivo and in Vitro Effects On Serotonergic Mechanisms. Naunyn Schmiedebergs Arch Pharmacol. 1993;347(3):306-12. PubMed PMID: 8479546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anorectic effect and brain concentrations of D-fenfluramine in the marmoset: relationship to the in vivo and in vitro effects on serotonergic mechanisms. AU - Caccia,S, AU - Anelli,M, AU - Fracasso,C, AU - Frittoli,E, AU - Giorcelli,P, AU - Gobbi,M, AU - Taddei,C, AU - Garattini,S, AU - Mennini,T, PY - 1993/3/1/pubmed PY - 1993/3/1/medline PY - 1993/3/1/entrez SP - 306 EP - 12 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 347 IS - 3 N2 - The present study investigated the anorectic activity of d-fenfluramine (d-F) and the relationship with brain levels of unchanged drug and its metabolite d-norfenfluramine (d-NF) in marmosets, relating them to neurochemical effects on the serotoninergic system. d-F and d-NF were equally active in reducing food intake (ED50 about 3 mg/kg, p.o.). However, the brain concentrations of the metabolite required to reduce food intake after synthetic d-NF were more than twice those after d-F, indicating that d-NF contributes to but does not completely explain the anorectic effect of d-F. At this dose d-F did not appreciably modify the serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) contents of the brain regions examined, except for a slight enhancement of 5-HIAA in hippocampus. In vitro in brain cortical synaptosomes d-F inhibited [3H]5-HT uptake more potently than d-NF, as in other species. d-F and d-NF showed similar potency in stimulating [3H]5-HT release, in a Ca++ dependent manner. The tritium released by d-F and d-NF appeared to be mainly unmetabolized [3H]5-HT. Like in other species the marmoset too has saturable and specific [3H]d-F binding sites, for which d-NF has lower affinity. d-F and d-NF have low affinities for 5-HT receptor subtypes, except that d-NF has appreciable affinity for 5-HT1C and 5-HT1D receptors. Unlike in rodents but similarly to primates in the striatum the pharmacology of 5-HT receptors seems to correspond to the 5-HT1D subtype.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0028-1298 UR - https://www.unboundmedicine.com/medline/citation/8479546/Anorectic_effect_and_brain_concentrations_of_D_fenfluramine_in_the_marmoset:_relationship_to_the_in_vivo_and_in_vitro_effects_on_serotonergic_mechanisms_ DB - PRIME DP - Unbound Medicine ER -