Therapeutic potential of melatonin agonists

Abstract

Melatonin, a hormone secreted by the pineal gland, has been successfully employed to improve sleep in both normal patients and insomniacs, and for the treatment of circadian rhythm sleep disorders. Melatonergic MT₁ and MT₂ receptors exist in high concentrations in the suprachiasmatic nucleus of the hypothalamus and have been shown to be instrumental for the sleep-promoting and circadian rhythm-regulating effects of melatonin. A lack of consistency among reports on the therapeutic efficacy of melatonin has been attributed to differences in melatonin’s bioavailability and the short half-life of the hormone. In view of the need for longer acting melatonergic agonists that improve sleep efficiency without causing drug abuse or dependency, ramelteon (Rozerem™, Takeda) was developed. Ramelteon, which acts via MT₁/MT₂ melatonergic agonism, has been found clinically effective for improving total sleep time and sleep efficiency in insomniacs. Agomelatine (Valdoxan™, Servier) is another MT₁/MT₂ melatonergic agonist that also displays antagonist activity at 5-HT_2C serotonin receptors. Agomelatine has been found effective in treating depression and sleep disorders in patients with major depressive disorder. A slow-release preparation of melatonin (Circadin™, Neurim) has been shown to be effective in treating sleep disorders in the elderly population.

Keywords::

• agomelatine
• antidepressant
• Circadin^®
• insomnia
• major depressive disorder
• melatonin
• melatonin receptors
• ramelteon

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.