The constitutive activity of different serotonin receptors (5-HTRs) toward intracellular signaling pathways has been proposed to have physiological and pathological importance. Inverse agonists block the constitutive activity and can be used to probe and silence such a spontaneous activity. The constitutive activity of 5-HTRs can be observed in various heterologous systems of expression in vitro (very high for 5-HT2CR; very low for 5-HT2AR). The demonstration of the existence of this activity in native tissues and ultimately in integrative neurobiology and behavior is a real pharmacological challenge. Irrespective of the existence of mutants or polymorphisms that could alter the constitutive activity of 5-HTRs, evidence suggests that spontaneous activity of 5-HT2CR could impact the activity of neurobiological networks and that of 5-HT6R and 5-HT7R the developmental morphogenesis. Some findings exist for 5-HT2BR and 5-HT2AR in diverse though rare conditions. The existence of a constitutive activity for 5-HT1AR, 5-HT1B/1DR, and 5-HT4R is still poorly supported. When identified, the constitutive activity may differ according to brain location, state of activity (phasic in nature), and intracellular signaling pathways. A very few studies have reported aberrant constitutive activity of 5-HTRs in animal models of human diseases and patients. The purpose of this review is a critical examination of the available neuropharmacological data on the constitutive activity of 5-HTRs to determine whether this activity is an essential component of the serotonergic system transmission and it may be a possible target for CNS drug development.

中文翻译：

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5-HT受体的组成活性：事实分析。

已经提出了不同的5-羟色胺受体（5-HTR）对细胞内信号传导途径的组成活性具有生理和病理学重要性。反向激动剂阻断了本构活性，可用于探测和沉默这种自发活性。可以在体外的各种异源表达系统中观察到5-HTR的组成性活性（对于5-HT2CR非常高；对于5-HT2AR非常低）。天然组织中这种活性的存在以及最终在整合神经生物学和行为中的存在的证明是真正的药理学挑战。无论是否存在可以改变5-HTR组成型活性的突变体或多态性，证据表明5-HT2CR的自发活性可能影响神经生物学网络的活性，而5-HT6R和5-HT7R的自发活性可能影响发育形态发生。在5-HT2BR和5-HT2AR的各种情况下（尽管罕见），存在一些发现。仍然很少支持5-HT1AR，5-HT1B / 1DR和5-HT4R的本构活性的存在。识别后，组成性活动可能会因大脑位置，活动状态（本质上是阶段性的）和细胞内信号传导途径而异。极少数研究报道了在人类疾病和患者的动物模型中5-HTR的异常组成性活性。