TOKYO, Japan — A drug which treats chronic alcoholism may find a new role helping patients overcome anxiety, a new study reveals. Researchers at the Tokyo University of Science say disulfiram, an FDA-approved alcoholism treatment, also has the ability to reduce anxiety levels in mice. The team is hopeful this will soon allow doctors to repurpose the drug for older adults dealing with anxiety and insomnia.
The study finds disulfiram (DSF) inhibits chemokine receptor signaling pathways, which play a key role in regulating feelings of anxiety in rodents. DSF has been such a successful treatment for alcoholism because it inhibits the enzyme aldehyde dehydrogenase (ALDH), which is responsible for metabolizing alcohol.
Previous studies examining disulfiram have also found that the drug inhibits a cytoplasmic protein called FROUNT. This protein controls the direction in which immune cells migrate. The drug prevents FROUNT from interacting with two chemokine receptors — CCR2 and CCR5. Both are important in cellular signaling pathways.
To find out if the chemokine receptors help to regulate emotional behavior, researchers placed mice in an elevated plus-maze (EPM) used to examine the effectiveness of other anxiety drugs. The maze features four arms in a cross pattern which connect in a central square. Two arms have vertical boundaries for protection and two do not. Typically, mice suffering from anxiety prefer to spend more time in the protected, closed arms of the maze.
Study authors compared the effect of taking common anxiety drugs like diazepam to mice taking DSF. Results show mice on disulfiram spent significantly more time in the unprotected parts of the maze than mice taking standard anxiety treatments.
How exactly does disulfiram treat anxiety?
In a previous study, the Japanese team discovered that mice with high anxiety displayed increased extracellular glutamate levels. This is an important amino acid and neurotransmitter.
“We propose that DSF inhibits FROUNT protein and the chemokine signaling pathways under its influence, which may suppress presynaptic glutamatergic transmission in the brain,” says Prof. Akiyoshi Saitoh in a university release. “This, in turn, attenuates the levels of glutamate in the brain, reducing overall anxiety.”
Moreover, the team found DSF treatments did not cause adverse side-effects such as amnesia or coordination disorders like diazepam does.
“These results indicate that DSF can be used safely by elderly patients suffering from anxiety and insomnia and has the potential to become a breakthrough psychotropic drug,” Prof. Saitoh adds.
“We plan to further clarify how DSF exerts its pharmaceutical actions. Hopefully, we will also be able to elucidate the exact role of the FROUNT molecule in the central nervous system.”
The findings are published in the journal Frontiers in Pharmacology.