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J Korean Sleep Res Soc > Volume 8(2); 2011 > Article
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J Korean Sleep Res Soc. 2011;8(2):25-30.         doi: https://doi.org/10.13078/jksrs.11007
새로운 멜라토닌성 약물들
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순천향대학교 의과대학 임상약리학교실
 
New Melatonergic Agents
Hyung Ki Kim
Department of Clinical Pharmacology, Soonchunhyang University College of Medicine, Cheonan, Korea
Corresponding Author: Hyung Ki Kim ,Tel: +82-41-570-2452, Fax: +82-41-576-6774, Email: hkkim@sch.ac.kr
Received: December 1, 2011   Accepted: December 29, 2011   Published online: December 31, 2011
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ABSTRACT
Melatonin is a major chronobiological regulator and has been used for the treatment of sleep problems including insomnia, parasomnia, and circadian rhythm sleep disorders. Because of melatonin’s short half-life, its suitability as a drug is limited. Thus, the development of prolonged-release melatonin and other melatonergic receptor agonists with a longer duration of action were needed. Ramelteon, non-indolic melatonergic agonist is the first drug approved in the USA for the treatment of insomnia. It showed highly selective melatonin MT1/MT2 receptor affinities which are believed to mediate the circadian rhythm whereas, negligible affinity for the MT3 receptor and other receptors in brain. This selective receptor affinity may explain the lack of significant adverse effect and lack of dependency or drug abuse potential. Another non-indolic melatonergic agonist is agomelatine initially evaluated for its chronobiotic effect. After its serotonergic effect was discovered, it was investigated as an antidepressant. There are studies indicating usefulness in controlling anxiety disorder and in seasonal affective disorder. Some studies showed agomelatine has a potential usefulness in improving sleep architecture. Tasimelteon is also an non-indolic melatonergic agonist which has high affinity for both MT1/MT2 receptors in humans and showed a similar affinity to melatonin. TIK-301, an indolic melatonin analogue also displays a high affinity towards melatonin MT1/MT2 receptors. Recently, TIK-301 has been shown that it also acts as an antagonist of the serotonin receptor subtype 5-HT2B and 5-HT2c, more potent than agomelatine. To elucidate efficacy and safety of newly developed melatonergic drugs, longer term multicenter clinical trials are needed.
Keywords: Melatonin receptor agonist | Agomelatine | Ramelteon | Tasimelteon | TIK-301.
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