TY - JOUR
T1 - Antagonism of ethanol withdrawal convulsions in withdrawal seizure prone mice by diazepam and abecarnil
AU - Crabbe, John C.
N1 - Funding Information:
These studies were supported by a grant from the US Department of Veterans Affairs. by grants from the USP!IS (AAO624.3. AAOXb2I. DAtii22X). and USPHS-NIDA Contract No. 271-90-7405. I thank Catherine Merrill for her expert help with these experiments. and Drs. David N. Stephens and Graham Jones (Schering-Berlin) for their comments on the manuscript.
PY - 1992/10/6
Y1 - 1992/10/6
N2 - Abecarnil, a β-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.
AB - Abecarnil, a β-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.
KW - (Genetic animal model)
KW - Abecarnil
KW - Anticonvulsant effects
KW - Diazepam
KW - Ethanol withdrawal
KW - Handling-induced convulsions
KW - Withdrawal seizure prone mouse (WSP)
KW - β-Carbolines
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U2 - 10.1016/0014-2999(92)90775-Y
DO - 10.1016/0014-2999(92)90775-Y
M3 - Article
C2 - 1360903
AN - SCOPUS:0026767539
SN - 0014-2999
VL - 221
SP - 85
EP - 90
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -