The introduction of atypical antipsychotics (AAPs) since the discovery of its prototypical drug clozapine has been a revolutionary pharmacological step for treating psychotic patients as these allow a significant recovery not only in terms of hospitalization and reduction in symptoms severity, but also in terms of safety, socialization and better rehabilitation in the society. Regarding the mechanism of action, AAPs are weak D₂ receptor antagonists and they act beyond D₂ antagonism, involving other receptor targets which regulate dopamine and other neurotransmitters. Consequently, AAPs present a significant reduction of deleterious side effects like parkinsonism, hyperprolactinemia, apathy and anhedonia, which are all linked to the strong blockade of D₂ receptors.

This review revisits previous and current findings within the class of AAPs and highlights the differences in terms of receptor properties and clinical activities among them. Furthermore, we propose a continuum spectrum of “atypia” that begins with risperidone (the least atypical) to clozapine (the most atypical), while all the other AAPs fall within the extremes of this spectrum.

Clozapine is still considered the gold standard in refractory schizophrenia and in psychoses present in Parkinson's disease, though it has been associated with adverse effects like agranulocytosis (0.7%) and weight gain, pushing the scientific community to find new drugs as effective as clozapine, but devoid of its side effects. To achieve this, it is therefore imperative to characterize and compare in depth the very complex molecular profile of AAPs. We also introduce relatively new concepts like biased agonism, receptor dimerization and neurogenesis to identify better the old and new hallmarks of “atypia”.

Finally, a detailed confrontation of clinical differences among the AAPs is presented, especially in relation to their molecular targets, and new means like therapeutic drug monitoring are also proposed to improve the effectiveness of AAPs in clinical practice.

自发现其典型药物氯氮平以来，非典型抗精神病药（AAPs）的引入已成为治疗精神病患者的革命性药理步骤，因为这些药物不仅可在住院治疗和减轻症状严重性方面，而且在安全性方面均具有显着的恢复，社会化和社会上更好的康复。关于作用机理，AAP是弱的D ₂受体拮抗剂，它们的作用超出了D _2的拮抗作用，涉及调节多巴胺和其他神经递质的其他受体靶标。因此，AAPs显着减少了有害的副作用，如帕金森氏症，高泌乳素血症，冷漠和​​快感不足，这些都与D ₂的强烈阻滞有关。 受体。

这篇评论回顾了AAP类中以前和当前的发现，并强调了它们之间在受体特性和临床活动方面的差异。此外，我们提出了一个“非典型性”连续谱图，该谱图从利培酮（非典型性）到氯氮平（非典型性）开始，而所有其他AAP都属于该极限。

氯氮平仍被认为是难治性精神分裂症和帕金森氏病所致精神病的金标准，尽管它与粒细胞缺乏症（0.7％）和体重增加等不良反应相关，促使科学界寻找与氯氮平同样有效的新药，但是没有副作用。为此，必须表征和深入比较AAP的非常复杂的分子谱。我们还引入了相对较新的概念，例如偏向激动性，受体二聚化和神经发生，以更好地识别“非典型性”的新旧标志。

最后，详细介绍了AAP之间临床差异的对立面，特别是与它们的分子靶标有关，并且还提出了新的手段，例如治疗药物监测，以提高AAP在临床实践中的有效性。