10-Butyl Ether Minocycline (BEM) Reduced Ethanol Consumption in Binge Drinking Mice

Abstract

Alcohol use disorder (AUD) is a complex brain disease with high morbidity, mortality, and limited treatment options, causing significant societal burden. Minocycline, well known for its anti-inflammatory and immunomodulatory properties, could potentially treat AUD but its antimicrobial activity would be inessential, and even a liability, for long-term treatment in AUD patients. 10-Butyl Ether Minocycline (BEM) was synthesized to retain minocycline's off-target actions and eliminate antimicrobial properties. We hypothesized that BEM would reduce high ethanol consumption in common murine models of binge drinking without affecting ethanol elimination. The Drinking-In-the-Dark (DID) paradigm was used to assess BEM's efficacy in reducing binge-like ethanol consumption. BEM dose-responsively reduced ethanol consumption in both female and male mice. Ethanol elimination following administration of both BEM and ethanol was evaluated using gas chromatography. BEM had no effect on ethanol metabolism in either sex, suggesting that its mechanism is independent and, thus, should not exacerbate ethanol-related toxicity when the two are taken together. Previous findings showed BEM effectively reduced chronic ethanol consumption. Future studies are underway to evaluate BEM's potential as an AUD treatment, which so far have shown BEM to be safer than minocycline and inexpensive to produce.