Cardiovascular effects of melatonin receptor agonists

Introduction: 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. Areas covered: 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. Expert opinion: The data suggest that cardiovascular effects of melatonin are at least partly mediated via MT1/MT2 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.