APR 21, 2022 2:31 PM PDT

Potential for New Anxiety Med in an Alcohol Dependence Drug

WRITTEN BY: Alexandria Bass

Don't look to alcohol to reduce your anxiety. Look to disulfiram, a drug that makes alcoholics sick when they drink alcohol.

A new study in Frontiers in Pharmacology headed by Akiyoshi Saitoh, PhD, a professor in the Department of Pharmacy at Tokyo University of Science, compared the effects of disulfiram to diazepam in mice during a stressful task. According to the study, disulfiram had similar effects to the classic anxiolytic diazepam.

Disulfiram is effective in treating alcohol dependence because it inhibits an enzyme that metabolizes alcohol, aldehyde dehydrogenase (ALDH). Without this enzyme to break down alcohol, disulfiram users who drink alcohol will experience unpleasant side effects such as nausea, vomiting, headache, chest pain, a fast heartrate, and even seizures and death if larger amounts of alcohol are consumed while taking the medication.

Along with inhibition of ALDH, disulfiram inhibits the cytoplasmic protein FROUNT. The inhibition of FROUNT is thought to decrease anxiety by reducing glutamate levels in the prelimbic-prefrontal cortex, increased levels of which in this brain region are associated with anxiety.

Interestingly, the investigators in this study report the discovery of disulfiram's anxiolytic effects was coincidental. The study was conducted as preclinical research on the secondary pharmacologic properties of disulfiram and not meant to study the anxiolytic effects of disulfiram from the outset. 

The researchers measured anxious behaviors in mice by subjecting them to an elevated plus-maze test. In this test, anxious mice will typically spend time in closed arms of the maze rather than open arms. Compared to controls that didn't receive diazepam or disulfiram, the mice that received disulfiram spent more time in the open arms of the maze the more disulfiram they received. These effects weren't seen in other ALDH inhibitors tested, like cyanamide. 

Disulfiram, compared to diazepam, may have its advantages. In a rotarod test in the study, a test of coordination where mice have to walk along a rotating rod, mice given disulfiram had no increases in the number of falls compared to diazepam-treated mice. 

This suggests disulfiram doesn't have the side effects of sedation, amnesia, and coordination impairments associated with diazepam and other benzodiazepines. Saitoh states the lack of these side effects may make disulfiram safe for elderly patients who need anxiety medications.

Sources: Medscape, Frontiers in Pharmacology, Everyday Health
 

About the Author
BA in Psychology
Alexandria (Alex) is a freelance science writer with a passion for educating the public on health issues. Her other professional experience includes working as a speech-language pathologist in health care, a research assistant in a food science laboratory, and an English teaching assistant in Spain. In her spare time, Alex enjoys cycling, lap swimming, jogging, and reading.
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