Neuroscience Postgraduate Program, Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
Neuroscience Postgraduate Program, Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
Pharmacol Biochem Behav. 2022 Jul;218:173422. doi: 10.1016/j.pbb.2022.173422. Epub 2022 Jun 19.
Although the rapid-onset and sustained antidepressant responses elicited by ketamine have gained considerable attention in recent years, it has some knock-on effects that limit its widespread clinical use. Therefore, ketamine is considered the prototype for the new generation of glutamate-based rapid-acting antidepressants. Within this context, it has been demonstrated that guanosine, an endogenous guanine-based purine, has overlapping mechanisms of action with ketamine and is effective in eliciting fast antidepressant-like responses and even potentiating ketamine's actions in preclinical studies. Here, we review the recent findings regarding the ability of guanosine to produce rapid-acting antidepressant-like effects and we provide an overview of the molecular mechanisms underlying its antidepressant-like actions. Moreover, the neurobiological mechanisms underpinning the ability of guanosine in boosting the antidepressant-like and pro-synaptogenic effects elicited by ketamine are also reported. Taken together, this review opens perspectives for the use of guanosine alone or in combination with ketamine for the management of treatment-resistant depression.
虽然氯胺酮引起的快速发作和持续抗抑郁反应近年来受到了相当大的关注，但它也有一些副作用，限制了其广泛的临床应用。因此，氯胺酮被认为是新一代基于谷氨酸的快速作用抗抑郁药的原型。在这种情况下，已经证明鸟苷，一种内源性基于鸟嘌呤的嘌呤，与氯胺酮具有重叠的作用机制，并且在临床前研究中有效引发快速抗抑郁样反应，甚至增强氯胺酮的作用。在这里，我们回顾了关于鸟苷产生快速抗抑郁样作用的最新发现，并提供了其抗抑郁样作用的分子机制概述。此外，还报告了鸟苷增强氯胺酮引起的抗抑郁样和促突触形成作用的神经生物学机制。总之，本综述为单独使用鸟苷或与氯胺酮联合治疗治疗抵抗性抑郁症开辟了前景。
