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[An experimental model of benzodiazepine intoxication]
E K Georgianova1, A V Lychakov, A M Malov
1Institute of Toxicology, Russian Federation Ministry of Public Health, St. Petersburg, Russia.
Eksperimental'Naia I Klinicheskaia Farmakologiia
|March 4, 1998
Summary
High-dose phenazepam causes prolonged autonomic and behavioral changes in rats, serving as a model for benzodiazepine (BD) intoxication. These effects were reversed by the BD antagonist flumazenil.
Area of Science:
- Pharmacology
- Neuroscience
- Toxicology
Context:
- Benzodiazepines (BDs) are widely prescribed medications with potential for overdose.
- Phenazepam is a potent benzodiazepine with significant central nervous system effects.
- Understanding severe BD intoxication is crucial for developing effective antidotes.
Purpose:
- To establish a rat model of severe phenazepam (a benzodiazepine) intoxication.
- To evaluate the utility of this model for testing potential antidote efficacy.
Summary:
- Intraperitoneal injection of 100 mg/kg phenazepam in rats induced prolonged immobilization, reduced muscle tone, impaired coordination, tachycardia, hypotension, hyperthermia, and disrupted motor activity and conditioned reflexes.
- These observed autonomic and behavioral changes were significant, long-lasting, and specific to benzodiazepine effects.
- The phenazepam-induced intoxication model was validated using the benzodiazepine antagonist flumazenil, demonstrating its efficacy in reversing the observed effects.
Impact:
- This study provides a validated animal model for severe benzodiazepine intoxication.
- The model can be used to screen and evaluate the efficacy of novel antidotes for benzodiazepine overdose.
- Findings contribute to a better understanding of benzodiazepine pharmacology and toxicology.