Capuzzi Enrico, Caldiroli Alice, Ciscato Veronica, Russo Stefania, Buoli Massimiliano
Psychiatric Department, Azienda Socio Sanitaria Territoriale Monza, Monza, Italy.
Department of Medicine and Surgery, University of Milano Bicocca, Monza, MB, 20900, Italy.
J Exp Pharmacol. 2021 Feb 5;13:49-67. doi: 10.2147/JEP.S259317. eCollection 2021.
Schizophrenia remains one of the most chronic and highly disabling mental disorder. To date, the pathomechanism of schizophrenia is not fully understood and current treatments are characterized by some limitations. First- and second-generation antipsychotics have shown clinical efficacy in treating positive symptoms, while are poorly effective on both negative symptoms and cognitive deficits. Moreover, they can involve many metabolic and neurological side effects, leading to low therapeutic compliance. Many evidence suggested that serotonin may play a complex role in the neurobiology of schizophrenia. Therefore, new drugs targeting 5-HT receptors (5-HTRs) have become an important area of research in schizophrenia in the hope that treatment efficacy may be improved without inducing side effects observed with currently available antipsychotics. Research using the main database sources was conducted to obtain an overview of preclinical and clinical pharmacological 5-HTR-targeted therapies in patients with schizophrenia. We identified 17 experimental serotonergic agents, under study for their potential use in schizophrenia treatment. Particularly, AVN-211, LuAF-35700 and Brilaroxazine are currently under clinical development. Moreover, some compounds showed some pro-cognitive and antipsychotic-like properties in animal models, while other agents showed contradictory effects in improving symptoms and were removed from the development program. Although some serotonergic drugs seem promising for improving the treatment of schizophrenia, further studies regarding the pathophysiological mechanisms of schizophrenia and novel compounds as well as high-quality trials are necessary in order to improve schizophrenia outcomes.
精神分裂症仍然是最具慢性和高度致残性的精神障碍之一。迄今为止，精神分裂症的发病机制尚未完全明了，当前的治疗方法存在一些局限性。第一代和第二代抗精神病药物在治疗阳性症状方面已显示出临床疗效，但对阴性症状和认知缺陷效果不佳。此外，它们可能会引发许多代谢和神经方面的副作用，导致治疗依从性较低。许多证据表明，血清素可能在精神分裂症的神经生物学中发挥复杂作用。因此，靶向5-羟色胺受体（5-HTRs）的新药已成为精神分裂症研究的一个重要领域，以期在不引发现有抗精神病药物所观察到的副作用的情况下提高治疗效果。我们利用主要数据库来源进行了研究，以全面了解精神分裂症患者中针对5-HTR的临床前和临床药理学治疗方法。我们确定了17种正在研究其在精神分裂症治疗中潜在用途的实验性血清素能药物。特别是，AVN-211、LuAF-35700和Brilaroxazine目前正处于临床开发阶段。此外，一些化合物在动物模型中显示出一些促认知和抗精神病样特性，而其他药物在改善症状方面显示出矛盾的效果，因此被从开发项目中剔除。尽管一些血清素能药物似乎有望改善精神分裂症的治疗，但为了改善精神分裂症的治疗效果，有必要进一步研究精神分裂症的病理生理机制、新型化合物以及高质量的试验。
