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Long-term treatment with abecarnil does not induce diazepam-like dependence in mice
K G Steppuhn1, H H Schneider, L Turski
1Research Laboratories of Schering AG, Berlin, Germany.
Summary
Abecarnil, a novel anxiolytic, does not cause dependence in mice, unlike benzodiazepines. This suggests abecarnil may be a safer long-term treatment for anxiety disorders.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Benzodiazepines are effective anxiolytics but can cause dependence.
- Abecarnil is a beta-carboline derivative with anxiolytic and anticonvulsant properties.
- Abecarnil binds to benzodiazepine receptors with high affinity.
Purpose of the Study:
- To evaluate the potential for abecarnil to induce dependence after chronic treatment in mice.
- To compare abecarnil's dependence-inducing potential with diazepam.
Main Methods:
- Chronic administration of abecarnil (6 mg/kg/day) or diazepam (15 mg/kg/day) to mice for 12 days.
- Electroencephalographic and electromyographic monitoring during withdrawal.
- Behavioral assessment of anxiety and muscle tone.
Main Results:
- Diazepam withdrawal induced anxiety, muscle rigidity, and seizures.
- Abecarnil withdrawal did not result in anxiety, seizures, or changes in muscle tone.
- Doses of abecarnil and diazepam were equivalent in receptor binding and kinetics.
Conclusions:
- Long-term abecarnil treatment does not induce benzodiazepine-like dependence in mice.
- Abecarnil represents a potential alternative to benzodiazepines for anxiety treatment with reduced dependence risk.