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Physical dependence on diazepam and lorazepam in the dog
The Journal of Pharmacology and Experimental Therapeutics
|September 1, 1983
Summary
This study found that both diazepam and lorazepam cause physical dependence in dogs, but withdrawal symptoms differ significantly. Diazepam withdrawal is more severe and involves distinct mechanisms compared to lorazepam withdrawal.
Area of Science:
- Pharmacology
- Neuroscience
- Veterinary Medicine
Background:
- Benzodiazepines like diazepam and lorazepam are widely prescribed.
- Physical dependence and withdrawal syndromes are significant concerns with chronic benzodiazepine use.
Purpose of the Study:
- To compare the physical dependence and withdrawal syndromes induced by diazepam and lorazepam in dogs.
- To investigate the underlying mechanisms of benzodiazepine withdrawal.
Main Methods:
- Dogs were chronically administered diazepam or lorazepam via gastric fistula.
- Abrupt drug discontinuation was followed by observation for abstinence signs using a Latin square crossover design.
- A benzodiazepine antagonist (CGS-8216) was administered to assess withdrawal mechanisms.
Main Results:
- Both diazepam and lorazepam induced withdrawal abstinence syndromes upon abrupt discontinuation.
- Diazepam withdrawal was more intense, longer-lasting, biphasic, and included lethal convulsions, unlike lorazepam withdrawal.
- A benzodiazepine antagonist precipitated abstinence in diazepam-dependent dogs but not in lorazepam-dependent dogs.
Conclusions:
- Diazepam and lorazepam induce distinct physical dependence and withdrawal syndromes.
- Diazepam withdrawal appears to involve multiple mechanisms, differing from lorazepam withdrawal.
- These findings highlight differential mechanisms in benzodiazepine dependence and withdrawal.