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Melatonin receptors as therapeutic targets in the suprachiasmatic nucleus

机译：褪黑素受体作为视交叉上核的治疗靶标

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Introduction: Disorders of rhythmicity can cause a variety of pathologies and are known to impair processes involved in metabolism, as well as in cardiovascular disease and cancer. Developing strategies to treat or prevent such diseases is a new challenge for medicine. Rhythms depend on a complex multi-oscillatory circadian network which, in mammals, is hierarchically organized with the suprachiasmatic nuclei (SCN) as master clock. The SCN, thus form an ideal structure for target discovery in circadian pathologies.Areas covered: The development of strategies to treat or prevent disorders of rhythmicity is a new challenge for medicine. Several pharmacological approaches have been suggested, but until now, it has been mostly melatonin (MTL) or MTL-agonists which have demonstrated usefulness in modulating clock activities in vivo. A great number of structurally different MTL receptor ligands have been developed, some of which are already approved and marketed as drugs. The MTL receptor involved in phase-shifting circadian rhythms (chronobiotic effect) is the MT1 subtype.Expert opinion: As the two receptor subtypes for MTL may have divergent functions, the development of highly selective MT1 and MT2 agonists (and antagonists) is key for the discovery of novel therapeutic agents in specifically defined circadian pathologies. The identification of cells expressing the different MTL receptor subtypes should also permit a better understanding of MLT physiology/pharmacology.
机译：简介：节律性疾病可导致多种病理，已知会损害新陈代谢以及心血管疾病和癌症的进程。制定治疗或预防此类疾病的策略是医学的新挑战。节律取决于复杂的多振荡昼夜节律网络，在哺乳动物中，其以视交叉上核（SCN）作为主时钟进行分层组织。因此，SCN形成了昼夜节律病理中靶标发现的理想结构。涵盖的领域：治疗或预防节律障碍的策略的发展是医学的新挑战。已经提出了几种药理学方法，但是直到现在，已经证明褪黑激素（MTL）或MTL激动剂主要用于调节体内的时钟活动。已经开发出许多结构上不同的MTL受体配体，其中一些已经被批准并作为药物销售。参与相移昼夜节律（时序生物效应）的MTL受体是MT1亚型。专家意见：由于MTL的两种受体亚型可能具有不同的功能，因此开发高度选择性的MT1和MT2激动剂（和拮抗剂）是MT1的关键。在明确定义的昼夜节律病理中发现新型治疗剂。表达不同MTL受体亚型的细胞的鉴定也应使人们更好地了解MLT生理学/药理学。

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