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The role of d-norfenfluramine in the indole-depleting effect of d-fenfluramine in the rat.
Eur J Pharmacol. 1993 Mar 16; 233(1):71-7.EJ

Abstract

The importance of d-norfenfluramine in regard to the indole-depleting action of d-fenfluramine has not been well studied in sensitive animal species. The present study therefore examined the intensity and time course of the neurochemical effects of i.p. injected d-fenfluramine (2.5 and 5 mg/kg) and d-norfenfluramine (2.5 mg/kg) in vehicle- and SKF-525A-pretreated rats, relating the effects to the brain concentration-time profiles of the drug and its active metabolite. At the lower dose d-fenfluramine caused only a small, short-lasting decrease in brain serotonin (5-HT) without affecting the 5-hydroxyindoleacetic acid (5-HIAA). Higher doses affected both 5-HT and 5-HIAA (50-60 and 30-40% reductions, respectively), the effect being maximal for at least 8 h. d-Norfenfluramine reduced the brain content of 5-HT and 5-HIAA less (by about 30%) than 5 mg/kg d-fenfluramine did. Brain concentrations of d-norfenfluramine at the time of the maximal depletion of indoles were close to those of the metabolite after 5 mg/kg d-fenfluramine, indicating that the acute indole-depleting effects did not depend solely on the brain concentrations of its nor-metabolite. SKF-525A changed the metabolite-to-parent drug ratios in brain without appreciably influencing the action of d-fenfluramine. However, the maximum decrease in indole content caused by 2.5 mg/kg d-fenfluramine in SKF-525A-pretreated rats was only 12% of the control level, although the brain concentration of unchanged drug was comparable to that after 5 mg/kg d-fenfluramine in vehicle-pretreated rats.(

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 available

Pub Type(s)

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

Language

eng

PubMed ID

7682511

Citation

Caccia, S, et al. "The Role of D-norfenfluramine in the Indole-depleting Effect of D-fenfluramine in the Rat." European Journal of Pharmacology, vol. 233, no. 1, 1993, pp. 71-7.
Caccia S, Anelli M, Ferrarese A, et al. The role of d-norfenfluramine in the indole-depleting effect of d-fenfluramine in the rat. Eur J Pharmacol. 1993;233(1):71-7.
Caccia, S., Anelli, M., Ferrarese, A., Fracasso, C., & Garattini, S. (1993). The role of d-norfenfluramine in the indole-depleting effect of d-fenfluramine in the rat. European Journal of Pharmacology, 233(1), 71-7.
Caccia S, et al. The Role of D-norfenfluramine in the Indole-depleting Effect of D-fenfluramine in the Rat. Eur J Pharmacol. 1993 Mar 16;233(1):71-7. PubMed PMID: 7682511.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of d-norfenfluramine in the indole-depleting effect of d-fenfluramine in the rat. AU - Caccia,S, AU - Anelli,M, AU - Ferrarese,A, AU - Fracasso,C, AU - Garattini,S, PY - 1993/3/16/pubmed PY - 1993/3/16/medline PY - 1993/3/16/entrez SP - 71 EP - 7 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 233 IS - 1 N2 - The importance of d-norfenfluramine in regard to the indole-depleting action of d-fenfluramine has not been well studied in sensitive animal species. The present study therefore examined the intensity and time course of the neurochemical effects of i.p. injected d-fenfluramine (2.5 and 5 mg/kg) and d-norfenfluramine (2.5 mg/kg) in vehicle- and SKF-525A-pretreated rats, relating the effects to the brain concentration-time profiles of the drug and its active metabolite. At the lower dose d-fenfluramine caused only a small, short-lasting decrease in brain serotonin (5-HT) without affecting the 5-hydroxyindoleacetic acid (5-HIAA). Higher doses affected both 5-HT and 5-HIAA (50-60 and 30-40% reductions, respectively), the effect being maximal for at least 8 h. d-Norfenfluramine reduced the brain content of 5-HT and 5-HIAA less (by about 30%) than 5 mg/kg d-fenfluramine did. Brain concentrations of d-norfenfluramine at the time of the maximal depletion of indoles were close to those of the metabolite after 5 mg/kg d-fenfluramine, indicating that the acute indole-depleting effects did not depend solely on the brain concentrations of its nor-metabolite. SKF-525A changed the metabolite-to-parent drug ratios in brain without appreciably influencing the action of d-fenfluramine. However, the maximum decrease in indole content caused by 2.5 mg/kg d-fenfluramine in SKF-525A-pretreated rats was only 12% of the control level, although the brain concentration of unchanged drug was comparable to that after 5 mg/kg d-fenfluramine in vehicle-pretreated rats.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/7682511/The_role_of_d_norfenfluramine_in_the_indole_depleting_effect_of_d_fenfluramine_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0014-2999(93)90350-Q DB - PRIME DP - Unbound Medicine ER -