Ramelteon-d5 (Synonyms: TAK-375-d5)

Ramelteon-d5 is intended for use as an internal standard for the quantification of ramelteon by GC- or LC-MS. Ramelteon is a melatonin (MT) receptor agonist (Kis = 14, 112, and 23.1 pM for human MT1, human MT2, and chick forebrain receptors, respectively). It is selective for MT1 and MT2 over MT3 receptors (Ki = 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. 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 learning and memory in the Morris water maze and delayed match-to-position tasks.