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[Cross tolerance when benzodiazepines are administered with other substances]
Biulleten' Eksperimental'Noi Biologii I Meditsiny
|June 1, 1981
Summary
Benzodiazepine drugs are uniquely responsible for complete cross-tolerance regarding muscle relaxation effects when combined with phenazepam. Other substances do not substitute phenazepam in developing this drug tolerance.
Area of Science:
- Pharmacology
- Neuroscience
Background:
- Phenazepam, a benzodiazepine, is known for its muscle relaxant properties.
- Drug tolerance, particularly cross-tolerance, is a significant factor in therapeutic efficacy and withdrawal.
- Understanding the mechanisms of benzodiazepine tolerance is crucial for developing safer and more effective treatments.
Purpose of the Study:
- To investigate the specificity of cross-tolerance to the myorelaxant effect of phenazepam.
- To determine which classes of drugs can substitute phenazepam in the development of tolerance.
- To explore potential mechanisms underlying benzodiazepine tolerance.
Main Methods:
- Experiments were conducted on rats to assess myorelaxant effects.
- Rats were treated with phenazepam to induce tolerance.
- Various substances, including other benzodiazepines, neuroleptics, ethanol, non-benzodiazepine tranquilizers, GABA receptor agonists, and potential endogenous ligands, were tested for cross-tolerance.
Main Results:
- Only drugs with a benzodiazepine structure induced complete cross-tolerance to phenazepam's myorelaxant effect.
- Neuroleptics, ethanol, phenobarbital, non-benzodiazepine tranquilizers, and muscimol did not cause cross-tolerance.
- Partial cross-tolerance was observed with nicotinamide, inosine, and calcium valproate.
Conclusions:
- Benzodiazepine structure is essential for complete cross-tolerance to phenazepam's myorelaxant effect.
- The findings suggest specific receptor interactions unique to benzodiazepines.
- Further research into the mechanisms of benzodiazepine tolerance is warranted.