[An experimental study of tolerance to benzodiazepines]

Rev Med Chir Soc Med Nat Iasi. 2002 Oct-Dec;106(4):806-11.
[Article in Romanian]

Abstract

The intention of the study was to demonstrate the appearance of the tolerance phenomenon after repeated administration of three of the most used benzodazepines (BDZ): Diazepam, Alprazolam and Oxazepam using three pharmacological tests, which monitored the neuromotor coordination, the myorelaxing and the anxiolitic effect. For each drug were used 3 doses, in geometrical progression, beginning with the partial dose, extrapolated from human to mouse according to the body surface. The treatment was made once a day, during 4 days. The appearance of tolerance was noticed, meaning an approximately 4-fold decrease of the sedative effect after the repeated administration of the 3 BDZ for all doses used. No tolerance was shown for the anxiolytic and myorelaxing effects, with the exception of alprazolam, which induced tolerance also for the myorelaxing effect. Our study has shown that repeated administration of BDZ might have different consequences on their pharmacological spectrum. The study indirectly explains the success of Alprazolam in therapy. This is due to the fact that small doses have approximately the some efficiency as the big ones in unique administration, decreasing the abuse potential. The rapid onset of the tolerance for the sedative and myorelaxing effect recommends its long-term administration in anxiolytic therapy.

Publication types

  • English Abstract

MeSH terms

  • Alprazolam / pharmacology
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Behavior, Animal / drug effects
  • Benzodiazepines / pharmacology*
  • Diazepam / pharmacology
  • Drug Tolerance
  • Mice
  • Models, Animal
  • Motor Activity / drug effects
  • Oxazepam / pharmacology

Substances

  • Anti-Anxiety Agents
  • Benzodiazepines
  • Oxazepam
  • Diazepam
  • Alprazolam