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Differences in the development of tolerance to various benzodiazepines
E Nowakowska1, A Chodera, D Cenajek-Musiał
1Department of Pharmacology, Medical Academy, Poznań, Poland.
Polish Journal of Pharmacology and Pharmacy
|May 1, 1987
Summary
Chronic administration of benzodiazepines like nitrazepam and chlordiazepoxide led to tolerance in sedative and anxiolytic effects. However, oxazepam showed no tolerance, and diazepam even demonstrated potentiated anticonvulsant action.
Area of Science:
- Pharmacology
- Neuroscience
Background:
- Benzodiazepines are widely used for their anticonvulsant, sedative, and anxiolytic properties.
- Understanding the development of tolerance to these effects with chronic administration is crucial for optimizing therapeutic use.
Purpose of the Study:
- To assess the anticonvulsant, sedative, and anxiolytic effects of chronic intraperitoneal administration of nitrazepam, diazepam, oxazepam, chlordiazepoxide, and temazepam.
- To investigate the development of tolerance to these effects across different benzodiazepines.
Main Methods:
- Chronic intraperitoneal administration of nitrazepam (NTZ), diazepam (DZ), oxazepam (OXZ), chlordiazepoxide (CDX), and temazepam (TMZ) in a study model.
- Assessment of anticonvulsant, sedative, and anxiolytic effects following repeated daily treatment.
Main Results:
- Nitrazepam exhibited rapid development of tolerance to sedative, anticonvulsant, and anxiolytic effects.
- Oxazepam showed no development of tolerance to its effects.
- Diazepam demonstrated a delayed stimulating effect but no tolerance to anxiolytic action, with even potentiated anticonvulsant effects.
- Chlordiazepoxide and temazepam rapidly developed stimulating actions and tolerance to anxiolytic effects, with only a slight decrease in anticonvulsant effects.
Conclusions:
- Benzodiazepine-induced tolerance varies significantly among different compounds and their effects.
- Oxazepam appears to be a promising agent for chronic use due to the absence of tolerance development.
- Diazepam's unique profile of delayed stimulation and potentiated anticonvulsant action warrants further investigation.