| Bioactivity | 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]. | ||||||||||||
| Target | IC50: 8 nM (CB1 receptor) | ||||||||||||
| Invitro | AM251 is a CB1 receptor antagonist/inverse agonist. AM251 produces an agonist response in HEK293 cells, similar to that found in the yeast expression system[2].AM-251 reduces cholesteryl ester synthesis in unstimulated and acetylated LDL-stimulated Raw 264.7 macrophages, CB2+/+ and CB2-/- peritoneal macrophages[3]. | ||||||||||||
| In Vivo | The CB1 antagonist AM251 (3 mg/kg, i.p.) decreases capsaicin-evoked nocifensive behavior. This suppressive effect is genotype dependent, and the interaction between the effects of genotype and AM251 approached significance. Planned comparisons reveal that AM251 reduces nocifensive behaviors in fatty-acid amide hydrolase (FAAH) KO mice (p0.2) relative to their respective vehicle controls. AM251 (3 mg/kg, i.p.) reduces the duration of heat hypersensitivity in FAAH KO (F1,9=21.43, p0.3). AM251 suppresses capsaicin-evoked heat hypersensitivity in a time-dependent manner in FAAH KO (F5,9=4.349, p0.3). Post-hoc analysis reveals that FAAH KO mice receiving vehicle (i.p.) display heightened thermal hypersensitivity at 30 (p<0.05), 60 (p<0.05), and 90 (p<0.001) minutes post-capsaicin in comparison to FAAH KO animals receiving AM251)[4].One-way ANOVA shows that AM251 (AM-251) injected into the rats significantly decreases both of the percentage of entries in the open arms and time spent in the open arms, compare to controls. The Tukey-Kramer test analysis reveals a significant reduction for the doses of 1 mg/kg (P<0.05) and 5 mg/kg (P<0.01) compare to control rats in the time spent in the open arms. Also, AM251 significantly decreases percentage of entries in the open arms for the doses of 1 and 5 mg/kg (P<0.05)[5]. | ||||||||||||
| Name | AM251 | ||||||||||||
| CAS | 183232-66-8 | ||||||||||||
| Formula | C22H21Cl2IN4O | ||||||||||||
| Molar Mass | 555.24 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
|
||||||||||||
| Reference | [1]. Bruno A, et al. Beyond radio-displacement techniques for identification of CB1 ligands: the first application of afluorescence-quenching assay. Sci Rep. 2014 Jan 20;4:3757. [2]. Sharir H, et al. Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol Ther. 2010 Jun;126(3):301-13. [3]. Thewke D, et al. AM-251 and SR144528 are acyl CoA:cholesterol acyltransferase inhibitors. Biochem Biophys Res Commun. 2009 Apr 3;381(2):181-6. [4]. Carey LM, et al. A pro-nociceptive phenotype unmasked in mice lacking fatty-acid amide hydrolase. Mol Pain. 2016 May 13;12. pii: 1744806916649192. [5]. Komaki A, et al. Study the Effect of Endocannabinoid System on Rat Behavior in Elevated Plus-Maze. Basic Clin Neurosci. 2015 Jul;6(3):147-53. [6]. Jiang X, et al. Role of cannabinoid receptor type 1 in tibial and pudendal neuromodulation of bladder overactivity in cats. Am J Physiol Renal Physiol. 2017 Mar 1;312(3):F482-F488. [7]. Sun L, et al. Endocannabinoid activation of CB1 receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation. Eur J Pain. 2017 May;21(5):804-814. |