Ramelteon

Ramelteon is a melatonin (MT) receptor agonist (K_is = 14, 112, and 23.1 pM for human MT₁, human MT₂, and chick forebrain receptors, respectively).¹ It is selective for MT₁ and MT₂ over MT₃ receptors (K_i = 2.65 μM for hamster brain MT₃ receptors) as well as a panel of benzodiazepine, dopamine, and opiate receptors, ion channels, transporters, and enzymes when used at a concentration of 10 μM. Ramelteon stimulates cAMP production in CHO cells expressing human MT₁ and MT₂ receptors (IC₅₀s = 21.2 and 53.4 pM, respectively). In vivo, ramelteon (0.03 and 0.3 mg/kg, p.o.) shortens latency to sleep onset and increases duration of sleep in free-moving crab-eating macaques.² It also accelerates reentrainment of circadian rhythm in rats, shifting running wheel activity back to the dark period 2.4 and 3 days more quickly than vehicle-treated animals following an eight-hour phase shift in the light-dark cycle when administered at 0.1 and 1 mg/kg, respectively, with no effect on learinng and memory in the Morris water maze and delayed match-to-position tasks.³

WARNING This product is not for human or veterinary use.

1. Kato, K., Hirai, K., Nishiyama, K., et al. Neurochemical properties of ramelteon (TAK-375), a selective MT₁/MT2 receptor agonist. Neuropharmacology 48(2), 301-310 (2005).

2. Yukuhiro, N., Kimura, H., Nishikawa, H., et al. Effects of ramelteon (TAK-375) on nocturnal sleep in freely moving monkeys. Brain Res. 1027(1-2), 59-66 (2004).

3. Hirai, K., Kita, M., Ohta, H., et al. Ramelteon (TAK-375) accelerates reentrainment of circadian rhythm after a phase advance of the light-dark cycle in rats. J. Biol. Rhythms 20(1), 27-37 (2005).