Isobolographic assessment of the effects of combinations of phenylpropanolamine and fenfluramine on food intake in rats

Paul J. Wellman, Sharon Tow, Lance McMahon

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Phenylpropanolamine (PPA) suppresses appetite in rats via activation of α1-adrenergic receptors within the paraventricular hypothalamus (PVN). The serotonergic (5-HT) agonist fenfluramine (FEN) is thought to suppress appetite via stimulation of 5-HT release within the PVN rather than activation of adrenergic receptors. Whether a mixture of these neurochemically distinct anorexic drugs will serve as an effective appetite suppressant is unknown. In the present experiment, drug-drug interactions between PPA and FEN were explored using an isobologram technique. Fixed doses of PPA (0 vs. 5 mg/kg) were combined with various doses of FEN (1.25, 2.5, and 5.0 mg/kg) and fixed doses of FEN (0 vs. 2.5 mg/kg) were combined with various doses of PPA (0, 5, 10, and 15 mg/kg). Drug combinations were injected IP 30 min before a 1-h feeding trial in 16-h food-deprived rats. PPA and FEN were dose-additive in this paradigm, an outcome that supports the feasibility of a new appetite suppressant composed of a mixture of PPA and FEN.

Original languageEnglish (US)
Pages (from-to)287-291
Number of pages5
JournalPharmacology, Biochemistry and Behavior
Volume50
Issue number2
DOIs
StatePublished - Feb 1995

Keywords

  • Anorexia
  • Feeding
  • Fenfluramine
  • Paraventricular hypothalamus
  • Phenylpropanolamine
  • Serotonin
  • α-Adrenoceptors

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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