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| 产品名称 | CB1 ↓ ↑ | CB2 ↓ ↑ | 其他靶点 | 纯度 | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Otenabant HCl | ++++ rCB1, Ki: 2.8 nM hCB1, Ki: 0.7 nM | 98+% | |||||||||||||||||
| AM251 | ✔ | 98% | |||||||||||||||||
| Rimonabant | +++ hCB1, IC50: 13.6 nM | ++ hCB2, IC50: 1.64 μM | 99% | ||||||||||||||||
| 1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。 | |||||||||||||||||||
| 靶点 | 
 | 
| 描述 | AM251 is a selective cannabinoid 1 (CB1) receptor antagonist with an IC50 of 8 nM. AM251 also acts as a potent GPR55 agonist with an EC50 of 39 nM[1].[2].[3]. | 
| 体内研究 | AM251, at a dosage of 3 mg/kg administered intraperitoneally, significantly decreases capsaicin-evoked nocifensive behavior in a genotype-dependent manner. AM251 (3 mg/kg, i.p.) reduces the duration of heat hypersensitivity in FAAH KO but not WT mice. AM251 suppresses capsaicin-evoked heat hypersensitivity in a time-dependent manner in FAAH KO but not in WT mice. Post-hoc analysis reveals that FAAH KO mice receiving vehicle (i.p.) display heightened thermal hypersensitivity at 30, 60, and 90 minutes post-capsaicin in comparison to FAAH KO animals receiving AM251)[4]. Furthermore, AM251 influences anxiety-related behaviors in rats, as indicated by its impact on open arm entries and time spent in the open arms of an elevated plus maze. Significant reductions in these measures were noted at doses of 1 mg/kg and 5 mg/kg, suggesting anxiogenic effects at these concentrations[5]. | 
| 体外研究 | AM251 shows an agonist response in HEK293 cells, similar to that found in the yeast expression system[2]. In macrophages, both unstimulated and stimulated by acetylated LDL, AM251 reduces cholesteryl ester synthesis. This effect is observed regardless of the presence or absence of CB2 receptors, indicating a broader scope of action beyond just cannabinoid receptor interaction[3]. | 
| Concentration | Treated Time | Description | References | |
| PANC-1 | 5 mM | 24 hours | AM251 induced significant increases in EGFR and HB-EGF mRNA levels. | Br J Pharmacol. 2011 Oct;164(3):1026-40. | 
| TG neurons | 10 µM | 3 minutes | To evaluate the activation of TG neurons by AM251 and AM630, results showed that AM251 and AM630 activated TG neurons in a concentration-dependent manner, with AM630 being more potent than AM251. | Neuropharmacology. 2011 Sep;61(4):778-88. | 
| Human and mouse islets | 10 µM | 48 hours | AM251 promotes β-cell proliferation and reduces apoptosis. | Cell Mol Life Sci. 2020 Nov;77(22):4709-4723. | 
| Rat dorsal raphe nucleus 5-HT neurons | 1 µM | at least 5 minutes | AM251 inhibited the firing rate of about 50% of all the recorded DRN 5-HT neurons, and this inhibitory effect was prevented and reversed by the GABA A receptor antagonist picrotoxin, suggesting that CB1 receptors regulate 5-HT neurons through the GABAergic system. | Br J Pharmacol. 2009 Nov;158(6):1579-87. | 
| CHO cells | 25 µM | To evaluate the activation of TRPA1 and TRPV1 channels by AM251 and AM630, results showed that AM251 and AM630 could activate TRPA1 but not TRPV1 channels. | Neuropharmacology. 2011 Sep;61(4):778-88. | |
| Xenopus oocytes | 0.3 µM | AM251 significantly enhanced GABA-induced currents, with an enhancement of more than threefold. | Br J Pharmacol. 2012 Apr;165(8):2479-84. | |
| Xenopus oocytes | 1 µM | AM251 significantly enhanced GABA-induced currents, with an EC50 of 0.40 µM and a maximal potentiation of 881%. | Br J Pharmacol. 2012 Apr;165(8):2479-84. | 
| Administration | Dosage | Frequency | Description | References | ||
| Rats | Anxiety and food intake suppression | Intraperitoneal injection | 2.0, 4.0, 8.0 mg/kg | AM251 induced significant anxiogenic effects in the elevated plus maze and reduced locomotion. | Eur Neuropsychopharmacol. 2010 Feb;20(2):112-22 | |
| Mice and rats | Wild-type and TRPA1 null-mutant mice | Hindpaw injection | 30 μg | Single injection | To evaluate the modulation of CAP-induced thermal hyperalgesia by AM251 and AM630, results showed that AM630 significantly attenuated CAP-induced thermal hyperalgesia, while AM251 had no significant effect, and these effects were dependent on the TRPA1 channel. | Neuropharmacology. 2011 Sep;61(4):778-88. | 
| Sprague-Dawley rats | Burn injury model | Intrathecal or Intraperitoneal injection | 30 μg (intrathecally), 0.1 mg/kg or 1 mg/kg (intraperitoneally) | Once daily for 7 days | AM251 significantly attenuated mechanical allodynia and thermal hyperalgesia after burn injury, and the effects persisted beyond the administration period. | Anesthesiology. 2014 Dec;121(6):1311-9 | 
| NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 | 
| NCT03160326 | - | Recruiting | March 2020 | United States, California ... 展开 >> San Francisco VA Medical Center Recruiting San Francisco, California, United States, 94121 Contact: Julie Doyle 415-221-4810 ext 2597 Julie.Doyle2@va.gov Principal Investigator: Cynthia Delgado, MD United States, District of Columbia Washington DC VA Medical Center Recruiting Washington, District of Columbia, United States, 20422 Contact: Brian M Hoover, MS 202-745-8000 ext 55826 Brian.Hoover@va.gov Principal Investigator: Michael Harris-Love, DSc Sub-Investigator: Haniel Hernandez, DPT Sub-Investigator: Sholey Argani, MD Sub-Investigator: Marc Blackman, MD 收起 << | 
| 计算器 | ||||
| 存储液制备 |  | 1mg | 5mg | 10mg | 
| 1 mM 5 mM 10 mM | 1.80mL 0.36mL 0.18mL | 9.01mL 1.80mL 0.90mL | 18.01mL 3.60mL 1.80mL | |
| CAS号 | 183232-66-8 | 
| 分子式 | C22H21Cl2IN4O | 
| 分子量 | 555.24 | 
| SMILES Code | O=C(C1=NN(C2=CC=C(Cl)C=C2Cl)C(C3=CC=C(I)C=C3)=C1C)NN4CCCCC4 | 
| MDL No. | MFCD01861181 | 
| 别名 | |
| 运输 | 蓝冰 | 
| 存储条件 | In solvent -20°C: 3-6个月 -80°C: 12个月 Pure form Keep in dark place, sealed in dry, store in freezer, under -20°C | 
| 溶解方案 | DMSO: 25 mg/mL(45.03 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO 以下溶解方案都请先按照体外实验的方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议现用现配,当天使用; 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 
 
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