Sieghart Werner
Center for Brain Research, Department of Molecular Neurosciences, Medical University Vienna, Spitalgasse 4, A-1090 Vienna, Austria.
Arch Pharmacol Ther. 2024 Jan;6(1):047. doi: 10.33696/Pharmacol.6.047.
α6-containing GABA receptors (α6GABARs) 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 α6GABARs (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.
含α6的GABA受体（α6GABARs）在小脑颗粒细胞中强烈表达，在那里它们介导执行行为的所有肌肉群的正确定时和精确协调，并保护大脑免受信息过载。最近，已证明对α6GABARs具有高选择性的正性调节剂（α6调节剂）在各自的动物模型中可将多种神经精神疾病的症状减轻到与既定临床治疗方法相当的程度。在此，对这些惊人的发现进行了讨论和解释。到目前为止，α6调节剂的有益作用及其缺乏副作用仅在各自疾病的动物模型中得到证实。临床前研究已证明它们适用于进一步的药物开发。未来的人体研究必须调查其安全性和可能的副作用，并阐明在急性和慢性给药期间，α6调节剂可在多大程度上减轻患者各自疾病的个体症状。由于其广泛的治疗潜力，α6调节剂可能成为多种神经精神疾病有价值的新治疗选择。
