Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108, Bratislava, Slovakia.
Expert Opin Investig Drugs. 2012 Nov;21(11):1661-78. doi: 10.1517/13543784.2012.714771. Epub 2012 Aug 23.
Melatonin synchronizes circadian rhythms with light/dark period and it was demonstrated to correct chronodisruption. Several melatonin receptor agonists with improved pharmacokinetics or increased receptor affinity are being developed, three of them are already in clinical use. However, the actions of melatonin extend beyond chronobiology to cardiovascular and metabolic systems as well. Given the high prevalence of cardiovascular disease and their common occurrence with chronodisruption, it is of utmost importance to classify the cardiometabolic effects of the newly approved and putative melatoninergic drugs.
In the present review, the available (although very sparse) data on such effects, in particular by the approved (circadin, ramelteon, agomelatine) or clinically advanced (tasimelteon, piromelatine = Neu-P11, TIK-301) compounds are summarized. The authors have searched for an association with blood pressure, vascular reactivity, ischemia, myocardial and vascular remodeling and metabolic syndrome.
The data suggest that cardiovascular effects of melatonin are at least partly mediated via MT(1)/MT(2) receptors and associated with its chronobiotic action. Therefore, despite the sparse direct evidence, it is believed that these effects will be shared by melatonin analogs as well. With the expected approval of novel melatoninergic compounds, it is suggested that the investigation of their cardiovascular effects should no longer be neglected.
褪黑素使昼夜节律与明暗周期同步，已被证明可纠正生物钟紊乱。目前正在开发几种具有改善的药代动力学或增加受体亲和力的褪黑素受体激动剂，其中三种已在临床应用。然而，褪黑素的作用不仅限于生物钟生物学，还延伸到心血管和代谢系统。鉴于心血管疾病的高发率及其与生物钟紊乱的常见发生，对新批准的和推测的褪黑素类药物的心脏代谢作用进行分类至关重要。
在本综述中，总结了现有（尽管非常稀少）关于这些作用的数据，特别是通过已批准的（circadin、ramelteon、agomelatine）或临床先进的（tasimelteon、piromelatine = Neu-P11、TIK-301）化合物获得的数据。作者搜索了与血压、血管反应性、缺血、心肌和血管重塑以及代谢综合征相关的作用。
数据表明，褪黑素的心血管作用至少部分是通过 MT(1)/MT(2)受体介导的，并与它的生物钟作用有关。因此，尽管直接证据很少，但人们认为这些作用也将被褪黑素类似物所共享。随着新型褪黑素类化合物的预期批准，建议不应再忽视对其心血管作用的研究。
