Ramelteon 是强效高选择性和可口服的MT1/MT2激动剂,Ki值分别为 14 和 112 pM,有用于失眠症的研究潜力。
产品描述
Ramelteon is a Melatonin Receptor Agonist. The mechanism of action of ramelteon is as a Melatonin Receptor Agonist.
体外活性
Ramelteon(0.03 mg/kg和0.3 mg/kg,p.o.)显著缩短了入睡潜伏期,并显著增加了自由活动猴子的总睡眠时间,且不影响猴子的日常行为.腹腔注射给药大鼠10 mg/kg Ramelteon,显著降低降低大鼠的NREM睡眠潜伏期,并且还产生非快速眼动(NREM)睡眠持续时间的短暂增加,但是NREM功率谱未变.
体内活性
Ramelteon抑制非洲爪蟾的黑色素细胞色素颗粒聚集,pEC50为11.48。1 nM Ramelteon不仅增加MT1/MT2小脑颗粒细胞的ERK1/2磷酸磷酸化,也增加只含一个褪黑激素受体的小脑颗粒细胞的ERK1/2磷酸磷酸化。Ramelteon抑制forskolin刺激的cAMP产生,在CHO细胞中IC50为21.2 pM。 4P-PDOT阻断Ramelteon(1 nM)对MT1 KO小脑颗粒细胞的刺激作用,而luzindole则减弱Ramelteon(1 nM)在MT2 KO小脑颗粒细胞中的作用。Ramelteon与重组人MT1和MT2受体具有高亲和力,pKi分别为10.05和9.70。
激酶实验
cDNA encoding the human MT1 gene is introduced into CHO cells. Cells are harvested at confluence in Ca2+ and Mg2+ free Hanks' balanced salt solution containing 5 mM EDTA and collected by centrifugation. Cells are homogenized in ice-cold 50 mM Tris–HCl buffer, washed twice, pelleted, and stored at -30°C until the binding assays are conducted. Test compound and 40 pM 2-[ 125I]melatonin are mixed with the thawed homogenate in a total volume of 1 mL and incubated at 25°C for 150 min. The reaction is terminated by addition of 3 mL of icecold buffer followed by vacuum filtration on a Whatman GF/B. The filter is washed twice and radioactivity is counted by a g-counter[1].
Cas No.
196597-26-9
分子式
C16H21NO2
分子量
259.349
别名
雷美替胺;TAK-375
储存和溶解度
Ethanol:49 mg/mL (188.9 mM)
DMSO:49 mg/mL (188.9 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years