A drug that treats alcoholism may be the next anti-anxiety medication
A new study found that disulfiram, a drug used to treat chronic
alcoholism, can safely reduce anxiety levels in rodents
Date:
April 14, 2022
Source:
Tokyo University of Science
Summary:
Disulfiram is a drug used to treat chronic alcoholism. However,
studies suggest that it also inhibits chemokine receptor signaling
pathways that are associated with the regulation of anxiety in
rodents. Now, researchers show that disulfiram can effectively
reduce anxiety without causing any of the adverse effects that
are linked to other anxiolytic drugs. Thus, disulfiram could
potentially become a safe and effective anti-anxiety drug.
FULL STORY ========================================================================== Alcoholism, if left untreated, could have dangerous repercussions. Thus,
it is no surprise that there are a range of drugs developed to treat
this condition.
Of these drugs, disulfiram (DSF) is approved by the Food and Drug Agency
(FDA) for the treatment of alcoholism. DSF primarily inhibits the enzyme aldehyde dehydrogenase (ALDH), which is responsible for the metabolism
of alcohol.
========================================================================== Could the inhibitory effects of DSF extend to signaling molecules as well? According to recent studies, DSF in fact inhibits a cytoplasmic protein
known as FROUNT, which controls the direction in which certain immune
cells migrate.
DSF blocks FROUNT from interacting with two chemokine receptors known
as CCR2 and CCR5, which are involved in important cellular signaling
pathways.
A few studies suggest that chemokine receptors may be involved in the regulation of emotional behaviors in rodents. However, there is a lack
of data on the exact association between FROUNT-chemokine signaling
and DSF. To clarify this link, a team comprising Prof. Akiyoshi Saitoh
from Tokyo University of Science and other researchers from institutes
across Japan conducted a study examining the pharmacological properties
of DSF. The study, which was published online on March 7, 2022 in
Frontiers in Pharmacology, describes how the research team used an
elevated plus-maze (EPM) test -- which is used to screen for anxiolytic
drugs -- to study the effects of DSF in mice.
The EPM apparatus consists of four arms set in a cross pattern, connected
to a central square. Two arms are protected by vertical boundaries,
whereas two have unprotected edges. Usually, mice with anxiety prefer
to spend time in the closed arms.
In this case, some mice were administered diazepam (a drug commonly
used to treat anxiety) and others, DSF. These mice were then placed in
the EPM apparatus, and their activity was monitored. To their surprise,
the team found that mice treated with DSF spent significantly more time
in the open arms of the apparatus, which indicates that they were less
anxious. The team also tested the anxiolytic effects of a more potent
FROUNT inhibitor, known as DSF- 41, and observed similar results.
What's interesting is that these behavioral changes were similar to those observed in mice treated with diazepam. How exactly did DSF achieve this?
The team had previously discovered that increased extracellular glutamate (which is an important amino acid and neurotransmitter) levels are
associated with increased anxiety in mice.
"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. Saitoh. "This, in turn, attenuates
the levels of glutamate in the brain, reducing overall anxiety."
The team was also pleasantly surprised to find that in contrast with
diazepam, DSF treatment did not lead to adverse effects such as amnesia, coordination disorders, or sedation.
According to Prof. Saitoh, "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." What are the long-term implications of these results? Dr. Saitoh explains, "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." This is one of the first studies to
reveal that DSF exhibits anti-anxiety properties comparable to those of existing benzodiazepines without exhibiting any side effects observed
with benzodiazepines. Hopefully, DSF's inhibitory activity against FROUNT functioning could be explored for successful anxiolytic drug development.
========================================================================== Story Source: Materials provided by Tokyo_University_of_Science. Note:
Content may be edited for style and length.
========================================================================== Journal Reference:
1. Akiyoshi Saitoh, Yoshifumi Nagayama, Daisuke Yamada, Kosho Makino,
Toshinori Yoshioka, Nanami Yamanaka, Momoka Nakatani, Yoshino
Takahashi, Mayuna Yamazaki, Chihiro Shigemoto, Misaki Ohashi, Kotaro
Okano, Tomoki Omata, Etsuko Toda, Yoshitake Sano, Hideyo Takahashi,
Kouji Matsushima, Yuya Terashima. Disulfiram Produces Potent
Anxiolytic-Like Effects Without Benzodiazepine Anxiolytics-Related
Adverse Effects in Mice.
Frontiers in Pharmacology, 2022; 13 DOI: 10.3389/fphar.2022.826783 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/04/220414110731.htm
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