A Commentary on the Therapeutic Potential of Melatonin and Its Analogues in CNS Conditions

The hormone, melatonin, is secreted by the pineal gland in the mammalian brain. It plays an important role in the regulation of the circadian rhythm and the sleep-wake cycle. Now, melatonin is also recognized for its anti-oxidative and free radical scavenging functions, as well as being an important modulator of the anti-inflammatory response within the immune-pineal axis. Melatonin therefore can exert extensive influence over a wide range of psychophysiological functions - primarily through the activation of melatonin receptors: MT1 and MT2. Here, we briefly summarize the potential clinical applications of melatonin and its analogues and the suggestion that dysregulation of melatonin signalling in the brain constitutes as causal risk factor to neurodegenerative diseases and mood disorders. Clinical and preclinical evidence for the antidepression and antianxiety efficacy of melatonin and its synthetic analogues (e.g. agomelatine) is outlined. Mechanistically, the positive impact of melatonin on adult neurogenesis in the hippocampus has been linked to the observed mood-stabilizing effects of melatonin and its analogues according to the “neurogenic hypothesis” of antidepressant drug action. This together with the anti-inflammatory and anti-oxidative profile of melatonin may explain its unique therapeutic profile. Although there remain inconsistencies to be resolved, melatonin and its receptors are viable targets for the development of novel mood-stabilizing agents with fewer side effects. They could be viable alternatives for patients who cannot tolerate current antidepressant drugs as well as those who are not responding to current medication.