Antagonism of ethanol withdrawal convulsions in Withdrawal Seizure Prone mice by diazepam and abecarnil.
Abecarnil, a beta-carboline acting at benzodiazepine receptors, has been shown to have anxiolytic and anticonvulsant properties in a number of models. It has reduced muscle relaxant and incoordinating effects in comparison to diazepam. Given the wide clinical application of diazepam to prevent alcohol withdrawal seizures, a genetic animal model was employed to compare abecarnil with diazepam for its anti-withdrawal effects. Withdrawal Seizure Prone (WSP) mice, genetically selected to develop severe handling-induced convulsions after withdrawal from chronic ethanol treatment, were exposed to ethanol vapor for 24 h. WSP mice given doses of abecarnil or diazepam at the peak of withdrawal had significantly reduced handling-induced convulsion scores. While abecarnil was slightly more potent than diazepam, its effects were shorter-lasting. Similar results were seen in an experiment where withdrawal handling-induced convulsions were assessed after a single high-dose ethanol injection. Abecarnil and diazepam also reduced the smaller handling-induced convulsion scores seen in naive WSP mice. Single doses of abecarnil or diazepam did not lead to a rebound elevation of handling-induced convulsion scores suggestive of a withdrawal reaction.
Research Service, VA Medical Center, Portland, OR.
J C
JC
Crabbe
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D002243:Carbolines / Q000627:therapeutic use*; D003975:Diazepam / Q000627:therapeutic use*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D051379:Mice; D012640:Seizures / Q000517:prevention & control*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D002243:Carbolines; D000431:Ethanol; C062769:abecarnil; D003975:Diazepam