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Temporal differences in behavioral effect of fenfluramine and norfenfluramine
1Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272.
Pharmacology, Biochemistry, and Behavior
|March 1, 1990
Summary
Rats learned to distinguish the anorectic drug d,l-fenfluramine from its vehicle. Its metabolite, norfenfluramine, showed faster action and longer duration, suggesting it contributes to the drug’s effects.
Area of Science:
- Pharmacology
- Neuroscience
- Behavioral Science
Background:
- Anorectic drugs are used for weight management.
- Fenfluramine is an anorectic agent with known effects on neurotransmitters.
- Understanding the discriminative stimulus properties of drugs is crucial for pharmacology.
Purpose of the Study:
- To characterize the discriminative stimulus properties of d,l-fenfluramine in rats.
- To investigate the dose-dependency and stereoselectivity of fenfluramine's effects.
- To compare the time-course of action between fenfluramine and its metabolite, norfenfluramine.
Main Methods:
- Operant conditioning task in male rats using a fixed-ratio 10 schedule.
- Administration of d,l-fenfluramine and its isomers via intraperitoneal injection.
- Dose-response assessments to determine ED50 values.
- Time-course analysis of drug and metabolite effects.
Main Results:
- Rats successfully discriminated d,l-fenfluramine from its vehicle.
- Fenfluramine's stimulus properties were dose-dependent (ED50 = 0.8 mg/kg).
- The d-isomer was more potent (ED50 = 0.6 mg/kg) than the l-isomer (ED50 = 1.2 mg/kg).
- Norfenfluramine exhibited a faster onset and longer duration of action compared to fenfluramine.
Conclusions:
- Both stereoisomers of fenfluramine possess discriminative stimulus properties.
- Norfenfluramine, a metabolite of fenfluramine, plays a significant role in the parent drug's discriminative effects.
- These findings contribute to understanding the neuropharmacology of fenfluramine and its metabolite.