Melatonin is an indole hormone secreted by the pineal gland. It is a new drug for the treatment of sleep disorders. It plays a role in regulating circadian rhythm and sleeps through specific receptors.
Current Situation and Problems of Melatonin Treating Sleep Disorders
Melatonin (MT) is currently a melatonin drug, which is a sleep-regulating drug with melatonin as the active ingredient. For those with mild sleep disorders, the sleep-onset latency can be reduced and the sleep time can be prolonged. For those with severe sleep disorders, long-term repeated administration can be performed to achieve the effect of relieving sleep disorders. Although melatonin can regulate the sleep cycle, promote and improve sleep quality, and taking exogenous melatonin in a timely and appropriate amount is effective for insomnia and sleep disorders caused by the disturbance of the biological clock caused by the decrease in the secretion of melatonin, it is not effective for Alzheimer's disease. The efficacy of patients with sleep disturbance and secondary sleep disturbance was not very significant. And because the secretion pathway of melatonin in the body is the pineal gland→of melatonin→heart-brain→liver, the existence of the first-pass effect leads to poor absorption effect of oral supplementation of melatonin, although some studies have pointed out that it can be used. The sublingual method improves the absorption rate of melatonin, but its effect is still not very obvious. Therefore, if melatonin is used as a sleep-regulating drug, the way of taking it still needs to be improved.
Supplementing exogenous melatonin needs to follow the body's natural melatonin secretion time, and it is best to take it 1 to 2 hours before going to bed. Melatonin has a short half-life and a short duration of action, and the effect of slow-release melatonin is relatively good. Although melatonin supplementation has a good effect and safety in regulating sleep in the short term, its long-term efficacy and safety still need further research.
What are Melatonergic drugs?
Melatonergic drugs have a long half-life, high absorption rate, and more obvious curative effects. Melatonergic drugs are mostly selective agonists, such as melatonin MT1 and MT2 receptors, and their affinity for the receptors is higher than that of melatonin. Activation of MT1 receptors can inhibit the activity of neurons in the suprachiasmatic nucleus (SCN), weaken the wake-up signal fed back by the SCN, and weaken the ability of the human body to promote wake-up by biological action, make sleep signals dominant, induce sleep and prolong sleep time. Activation of MT2 receptors enables the SCN to generate biofeedback signals to regulate the phase transition of sleep and restore the normal biological clock. Mainly include ramelteon, agomelatine, Tasimelteon (VEC-162) and PD6735 (TIK-301), piromelatine, Neu-P11.
Ramelteon is a selective melatonergic drug with a good curative effect on sleep disorders and few adverse reactions. It was approved by the US FDA for the treatment of insomnia in 2005. Selective affinity for MT1 and MT2 receptors is 1000 times that of melatonin. And it can take effect quickly, and the peak time of blood drug concentration is about 0. 3 h, mainly through hepatic CYP1A2 oxidative metabolism.
Agomelatine has a high affinity for melatonin receptors located in the central nervous system; in addition, it is also a serotonin (5-HT2C) receptor antagonist with a high affinity for 5-HT2C, can play antidepressant and sleep-promoting effects at the same time, and has no obvious adverse reactions, good tolerance, can be used as the drug of choice for depressive insomnia, in the treatment of depression-related sleep disorders can improve sleep efficiency, reduce sleep arousal, increase slow-wave Sleep, prolong REM sleep latency and normalize sleep structure. Therefore, it has been approved by the European Union as an antidepressant for clinical treatment.
Tasimelteon (VEC-162) and PD6735 (TIK-301) are both new melatonergic drugs, which are still in clinical research and have significant therapeutic effects on circadian biological rhythm sleep disorders. Tasimelteon can be used for acute insomnia in which the normal sleep cycle is disrupted.
Piromelatine, Neu-P11 is a new type of melatonin receptor agonist, which has an agonistic effect on 5-HT1A and 5-HT1D receptors, a lower antagonistic effect on 5-HT2B receptor, and is a multi-ion channel inhibitor.
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