ABSTRACT
ABSTRACT Daytime administration of exogenous melatonin (when it is not present endogenously) promotes sleep in humans and results in sleep-like brain activity patterns at specic areas such as the precuneus and hippocampus. However, existing studies on the hypnotic efcacy of melatonin have been highly heterogeneous in regard to inclusion and exclusion criteria, measures to evaluate insomnia, doses of the medication, and routes of administration. The inconsistent reports about the effectiveness of exogenous melatonin in the treatment of insomnia brought about the development of more potent melatonin analogs with prolonged effects and the design of slow-release melatonin preparations. The melatonergic receptor ramelteon is a selective melatonin-1 (MT1) and melatonin-2 (MT2) receptor agonist with negligible afnity for other neuronal receptors, including gamma-aminobutyric acid and benzodiazepine receptors. It was found effective in increasing total sleep time and sleep efciency as well as in reducing sleep latency in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT1 and MT2 melatonergic agonism and relatively weak serotonin 5HT2C receptor antagonism, reportedly is effective in the treatment of depression-associated insomnia.
