Ethosuximide Reduces Mortality and Seizure Severity in Response to Pentylenetetrazole Treatment During Ethanol Withdrawal.

Melissa A Riegle, Melissa L Masicampo, Hong Qu Shan, Victoria Xu, Dwayne W Godwin

Index: Alcohol Alcohol. 50 , 501-8, (2015)

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Abstract

We recently demonstrated that T-type calcium channels are affected by alcohol abuse and withdrawal. Treatment with ethosuximide, an antiepileptic drug that blocks T-type calcium channels, reduces seizure activity induced by intermittent ethanol exposures and withdrawals. Here, we expand on these findings to test whether ethosuximide can reduce the sensitivity to pentylenetetrazole-induced seizures during ethanol withdrawal.We used an intermittent ethanol exposure model to produce withdrawal-induced hyperexcitability in DBA/2J mice.Ethosuximide (250 mg/kg) reduced seizure severity in mice undergoing ethanol withdrawal with concurrent PTZ treatment (20 mg/kg). Importantly, ethosuximide did not produce rebound excitability and protected against ethanol withdrawal-induced mortality produced by concurrent PTZ treatment (40 mg/kg).These results, in addition to previous preclinical findings, suggest that ethosuximide should be further evaluated as a safe, effective alternative to benzodiazepines for the treatment of alcohol withdrawal.© The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.