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Codeine produces a cholinergically mediated analeptic effect in rats and rabbits
A Horita1, M A Carino, C Chinn
1Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
Pharmacology, Biochemistry, and Behavior
|May 1, 1988
Summary
Codeine shortens anesthesia duration in rabbits, an effect amplified by naltrexone. This suggests codeine
Area of Science:
- Pharmacology
- Neuroscience
Background:
- Benzodiazepines like diazepam induce anesthesia.
- Codeine's potential central nervous system effects are under investigation.
Purpose of the Study:
- To investigate the analeptic (wake-promoting) effects of codeine.
- To elucidate the mechanisms underlying codeine's interaction with anesthetics.
Main Methods:
- Intravenous administration of codeine and naltrexone to diazepam-narcotized rabbits.
- Assessment of narcosis duration.
- Testing the effects of atropine and methylatropine.
- Measurement of choline uptake in rat synaptosomes.
Main Results:
- Codeine shortened the duration of loss of righting reflex in rabbits.
- Naltrexone enhanced codeine's analeptic effect and shortened pentobarbital narcosis.
- Atropine blocked the analeptic effect, suggesting a central cholinergic mechanism.
- Analeptic activity correlated with reversal of reduced choline uptake in rats.
Conclusions:
- Codeine exhibits analeptic properties, potentially via central cholinergic pathways.
- Findings support a pharmacological basis for codeine's antinarcoleptic effects in humans.