Topiramate (Topamax) reduces conditioned abstinence behaviours and handling-induced convulsions (HIC) after chronic administration of alcohol in Swiss-Webster MICE

Farook, Justin M.; Morrell, Dennis J.; Lewis, Ben; Littleton, John M.; Barron, Susan

doi:10.1093/alcalc/agm047

Cited by 40 publications

(34 citation statements)

References 26 publications

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“…Further, topiramate also has been shown to suppress alcohol drinking moderately in both alcoholpreferring (P) and Wistar rats [131]. Additional to its ethanol-suppressing effects, there is evidence that topiramate can reduce alcohol withdrawal symptoms in a model of handling induced convulsions [132]. Hence, the preponderance of the animal literature does support topiramate as a promising medication for the treatment of alcohol dependence.…”

Section: Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid Andmentioning

confidence: 99%

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Johnson

2008

Biochemical Pharmacology

244

185

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The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)-approved medications naltrexone and acamprosate have shown mixed results in clinical trials. Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study. Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials. Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic. As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored.

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Section: Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid Andmentioning

confidence: 99%

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Johnson

2008

Biochemical Pharmacology

244

185

View full text Add to dashboard Cite

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“…The mechanism for this action is primarily due to their modulatory action on the BZ binding site of the gamma-aminobutyric acid-A (GABA-A) receptor [12]. In the present study, diazepam was used as a positive control due to its ability to reduce the HIC susceptibility during alcohol withdrawal using the HIC procedural test [13].…”

Section: Introductionmentioning

confidence: 99%

Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice

Farook

Krazem

Lewis

et al. 2008

Physiology & Behavior

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In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg) + methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1mg/kg (p's < 0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300mg/kg (p's < 0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence.

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“…Oxcarbazepine was as efficient as BZD to prevent seizures and reduce withdrawal symptoms and provided the advantages of lower side effects and easier tapering, but again the study population was small [36]. Topiramate, a large spectrum antiepileptic with GABAergic and antiNMDA activities, has demonstrated efficacy to prevent seizures and reduce withdrawal symptoms in rats and mice [37,38] and to prevent seizures (open label study, with only 12 patients) and to improve alcohol dependence in humans [39,40].…”

Section: Alcohol and Central Nervous System From Chronic Alcohol Intmentioning

confidence: 99%

“…Among newer AED: topiramate seems to present advantages to reduce alcohol-dependence [37][38][39][40], whereas levetiracetam failed [46]. Gabapentine needs more investigations to confirm a quite similar benefit, observed in rats but not in heavy drinking humans [47,48].…”

Section: From First Withdrawal Seizure To Epilepsymentioning

confidence: 99%

The Relationship between Alcohol and Seizures: An Overview of the Major Data

Visee¹

2015

Int J Neurorehabilitation Eng

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Topiramate (Topamax) reduces conditioned abstinence behaviours and handling-induced convulsions (HIC) after chronic administration of alcohol in Swiss-Webster MICE

Abstract: These findings suggest that topiramate reduces HICs during alcohol withdrawal and alcohol-conditioned behaviours during conditioned abstinence in Swiss-Webster mice.

Cited by 40 publications

References 26 publications

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice

The Relationship between Alcohol and Seizures: An Overview of the Major Data

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