Why Can Modulation of α6-Containing GABA A Receptors Reduce the Symptoms of Multiple Neuropsychiatric Disorders?

α6-containing GABA _A receptors (α6GABA _A Rs) are strongly expressed in cerebellar granule cells, where they mediate a correctly timed and precise coordination of all muscle groups that execute behavior and protect the brain from information overflow. Recently, it was demonstrated that positive modulators with a high selectivity for α6GABA _A Rs (α6-modulators) can reduce the symptoms of multiple neuropsychiatric disorders in respective animal models to an extent comparable with established clinical therapeutics. Here, these incredible findings are discussed and explained. So far, the beneficial actions of α6-modulators and their lack of side effects have only been demonstrated in animal models of the respective disorders. Preclinical studies have demonstrated their suitability for further drug development. Future human studies have to investigate their safety and possible side effects, and to clarify to which extent individual symptoms of the respective disorders can be reduced by α6-modulators in patients during acute and chronic dosing. Due to their broad therapeutic potential, α6-modulators might become a valuable new treatment option for multiple neuropsychiatric disorders.
Competing Interests: Conflict of Interest The author is one of the inventors from four different Universities who discovered the action of alpha6-selective allosteric modulators mentioned in this article. Together, the four Universities filed the U.S. Patent 10,865,203; U.S.Patent 11,427,582; and the European Patent 3325479, entitled: “Ligands selective to alpha6 subunit-containing GABAA receptors and their methods of use”. The patent rights are co-owned by the inventor´s institutions. The author has been retired for several years and has no relationship with any pharmaceutical company and no other competing interests.