Pharmacological characterization of M-II, the major human metabolite of ramelteon.
Pharmacology
; 93(3-4): 197-201, 2014.
Article
em En
| MEDLINE
| ID: mdl-24923230
ABSTRACT
The duration of action of melatonin may be important for improvements in sleep efficiency in insomniacs. Ramelteon, a selective melatonin agonist, is primarily metabolized to the active metabolite M-II, which has a longer half-life and greater systemic exposure than ramelteon. Hence, M-II may contribute significantly to the hypnotic benefits of ramelteon. We assessed the ramelteon-like activity of M-II in vitro and in vivo using cats. Binding and functional studies in Chinese hamster ovary cells expressing human melatonin receptors (MT1 or MT2) revealed that M-II binds melatonin receptors with lower affinity (Ki 114 and 566 pmol/l for MT1 and MT2, respectively) and has lower potency (IC50 208 and 1,470 pmol/l for MT1 and MT2, respectively) compared with ramelteon. However, higher M-II doses significantly improved sleep in cats. Thus, M-II may contribute to the clinical efficacy of ramelteon.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptor MT1 de Melatonina
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Receptor MT2 de Melatonina
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Hipnóticos e Sedativos
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Indenos
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article