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Acute tolerance to diazepam induced by benzodiazepines
Clinical and Experimental Pharmacology & Physiology
|January 1, 1986
Summary
Single exposure to diazepam or lorazepam decreased their sleep-inducing effects, indicating acute tolerance. Benzodiazepine antagonist RO 15-1788 did not cause tolerance, suggesting central nervous system changes may be involved.
Area of Science:
- Pharmacology
- Neuroscience
Background:
- Benzodiazepines like diazepam are widely used for their sedative and hypnotic effects.
- Understanding the development of tolerance to these drugs is crucial for clinical application.
Purpose of the Study:
- To investigate the development of acute tolerance to diazepam's sleep-inducing effects.
- To compare the effects of a benzodiazepine antagonist on tolerance development.
Main Methods:
- Assessing diazepam's effectiveness in inducing sleep (loss of righting reflex) after single exposures.
- Administering diazepam, lorazepam, and the benzodiazepine antagonist RO 15-1788.
Main Results:
- A single exposure to diazepam or lorazepam significantly reduced their subsequent sleep-inducing efficacy.
- The benzodiazepine antagonist RO 15-1788 did not induce tolerance to diazepam.
Conclusions:
- Acute tolerance to diazepam develops rapidly after a single exposure.
- Metabolic tolerance is unlikely given the speed of onset; altered brain sensitivity is a potential mechanism.