Alcohol use disorders
(AUDs) have great national effects that influence over 18 million people
and is responsible for over 100,000 deaths in the United States. Few
therapeutic options urge to introduce better effectual treatment. Dr.
Kelle M. Franklin and his
team from Indiana University School of Medicine have found the
relationship between the P2X4 receptor (P2X4Rs) and ethanol consumption
and suggested a potential clinical use of ivermectin (IVM) for the
treatment of AUDs. P2XR is known mostly as abundant ligand-gated
ion channels (LGICs) in the CNS. The ion channel is controlled by
extracellular ATP activation and influences important cellular
mechanisms such as neurotransmission and hormone secretion. The study
demonstrated that animal models with lower functional expression
of the P2RX4 gene showed more alcohol preference than others with the
higher functional expression of the gene. As a result, the experimental
group of mice lacking the gene drank more ethanol containing beverages
than the wild type controls. Otherwise, IVM
has a positive effect as a modulator of P2X4Rs in order to antagonize
the ethanol-mediated inhibition of P2X4Rs in vitro. As a result, it
reduces the tendency of ethanol intake in vivo.
Most treatment of AUDs attempt to block metabolism of alcohol intake or
to enhance neurochemical and neuropeptide systems for craving and
dependence. However, the field is still relatively new and there is
still much progress to be made. The study has suggested
that IVM would be a potential clinical tool for AUDs. IVM is already
approved by the FDA in the use of veterinary and clinical medicine. IVM
regulates a number of ion channels in terms of enhancing inhibitory
neurotransmission and reducing excitatory transmission.
So, the agonistic effect of IVM proposes to block P2X4Rs pathway and
eventually reduce the alcohol intake behavior of patients.
As in the case of all animal researches, animal models cannot be used to
fully cover a human. The P2X4R used in the study was cultured from
rats. In the human body, hP2X4 mostly corresponds to the specific gene
from a rat and it shares about 87% of the rat
polypeptide sequence. It is uncertain whether the finding would coincide
within human beings as it had been studied within only animal models.
Still, 13% of the difference in gene sequence remains a relatively large
difference in terms of genetics.
Abstract
Reference:
Franklin, K. M., Asatryan, L., Jakowec, M. W., Trudell, J. R., Bell, R.
L., & Davies, D. L. (2014). P2X4 receptors (P2X4Rs) represent a
novel target for the development of drugs to prevent and/or treat
alcohol use disorders. Front Neurosci, 8, 176. doi:
10.3389/fnins.2014.00176

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