Ramelteon metabolite M-II

• CAT Number: R009625
• CAS Number: 896736-21-3
• Molecular Formula: C16H21NO3
• Molecular Weight: 275.34
• Purity: ≥95%
• Synonyms: 2-hydroxy-N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzofuran-8-yl]ethyl]propanamide
• InChI: InChI=1S/C16H21NO3/c1-10(18)16(19)17-8-6-12-3-2-11-4-5-14-13(15(11)12)7-9-20-14/h4-5,10,12,18H,2-3,6-9H2,1H3,(H,17,19)/t10?,12-/m0/s1
• InChIKey: FGFNIJYHXMJYJN-KFJBMODSSA-N
• SMILES: CC(C(=O)NCCC1CCC2=C1C3=C(C=C2)OCC3)O

Ramelteon metabolite M-II is the major metabolite of Ramelteon, with IC50s of 208 pM, 1470 pM for human melatonin receptors (MT1 or MT2). Ramelteon is a selective melatonin agonist.
The affinity of Ramelteon metabolite M-II (M-II) for MT1 receptors is 10- and 2.5-fold lower than that of ramelteon and melatonin, respectively. Likewise, the affinity of M-II for MT2 receptors is approximately 5- and 1.5-fold lower than that of ramelteon and melatonin, respectively. Ramelteon metabolite M-II exhibits no affinity for quinone reductase 2 at concentrations up to 10 μM. Moreover, the selectivity of Ramelteon metabolite M-II for melatonin receptors relative to 215 targets including other receptors, transporters, ion channels and enzymes is investigated. Ramelteon metabolite M-II shows no significant affinities and activities for the other targets, except for the 5-HT2B receptor, for which the Ki value was 1.75±0.23 μM. The potency of Ramelteon metabolite M-II for MT1 receptors is approximately 17- and 4.3-fold lower than that of ramelteon and melatonin, respectively. Similarly, the potency of Ramelteon metabolite M-II for MT2 receptors is approximately 28- and 1.6-fold lower than that of ramelteon and melatonin, respectively[1].
Ramelteon metabolite M-II (1 mg/kg) significantly increases NREM sleep (F1,7=96.3, p<0.01) and significantly decreases wakefulness (F1,7=56.7, p<0.01). Moreover, a lower dose of M-II (0.1 mg/kg) yield similar results (NREM, F1,7=121.9, p<0.01; wakefulness, F1,7=87.0, p<0.01), and decreased wakefulness is sustained for 6 h after the administration of either dose. After the administration of 0.01 mg/kg Ramelteon metabolite M-II, only NREM sleep is significantly increased (F1,7=10.5, p< 0.05). No significant differences in REM sleep are observed after the administration of M-II at any of the doses tested in this study[1].

Reference

[1]. Nishiyama K, et al. Pharmacological characterization of M-II, the major human metabolite of ramelteon. Pharmacology. 2014;93(3-4):197-201.
 [Content Brief]