Caraci Filippo, Leggio Gian Marco, Salomone Salvatore, Drago Filippo
Department of Drug Sciences, University of Catania, Catania, Italy.
IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Troina (EN), Italy.
F1000Res. 2017 Mar 30;6:397. doi: 10.12688/f1000research.10233.1. eCollection 2017.
The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer's disease. All of the compounds considered were recently approved for human use or are in advanced clinical trials. Drugs included here are new antipsychotic medications endowed with a preferential affinity at dopamine D3 receptor (cariprazine) or at glutamatergic or cannabinoid receptors, as well as vortioxetine, a drug approved for managing the cognitive deficits associated with major depression. New mechanistic approaches for the treatment of depression include intravenous ketamine or esketamine or intranasal esketamine. As for Alzheimer's disease, the possible value of passive immunotherapy with agents such as aducanumab is considered to be a potential disease-modifying approach that could slow or halt the progressive decline associated with this devastating disorder.
近年来，具有新型作用机制的精神药物获批情况稀少。为解决这一问题，进一步分析神经精神疾病的病理生理学对于确定精神药物的新药理学靶点至关重要。在本报告中，我们详细介绍了正在作为精神疾病治疗药物进行研究的候选药物。特别强调了具有新型作用机制、正在作为抑郁症、精神分裂症或阿尔茨海默病治疗方法进行测试的药物。所有考虑的化合物最近均已获批用于人体或正处于晚期临床试验阶段。此处纳入的药物包括对多巴胺D3受体（卡立普唑）或谷氨酸能或大麻素受体具有优先亲和力的新型抗精神病药物，以及已获批用于治疗与重度抑郁症相关认知缺陷的药物伏硫西汀。治疗抑郁症的新机制方法包括静脉注射氯胺酮或艾氯胺酮或鼻内给予艾氯胺酮。至于阿尔茨海默病，使用如阿杜卡单抗等药物进行被动免疫治疗的潜在价值被认为是一种可能改变疾病进程的方法，可减缓或阻止与这种毁灭性疾病相关的进行性衰退。
