AM1241 is an aminoalkylindole analog and a selective ligand for the type II cannabinoid receptor (CB2), exhibiting higher affinity for the CB2 receptor (Ki=3.4nM) than for the CB1 receptor (Ki=280nM)[1-2]. AM1241 is applicable in research related to neuropathic pain and inflammatory pain[3-4].
In vitro, AM1241 (4μM) combined with LBH589 (0.1μM) was administered to cervical cancer SiHa cells for 24 hours. AM1241 synergized with LBH589 to significantly inhibit cell proliferation and induce apoptosis. AM1241 activated the endoplasmic reticulum stress pathway, DNA damage repair signaling pathways, the autophagy pathway, and increased reactive oxygen species (ROS) levels[5]. AM1241 (5-20μM) was used to pretreat BV2 microglial cells for 1 hour, followed by stimulation with H₂O₂ (1mM) for 4 hours. AM1241 significantly inhibited H₂O₂-induced release of pro-inflammatory factors TNF-α and IL-6, ROS production, and the formation of the MD2/TLR4 complex, while also reducing apoptosis7[6].
In vivo, AM1241 (6mg/kg) was intraperitoneally administered to Sprague-Dawley rats with myocardial ischemia-reperfusion injury (a single dose given 1 hour before modeling). AM1241 significantly improved cardiac function indicators (left ventricular ejection fraction and fractional shortening), reduced myocardial infarction area, decreased serum levels of myocardial injury markers (cTnI, AST, LDH, CK-MB), and attenuated oxidative stress and apoptosis[7]. AM1241 (3mg/kg or 9mg/kg) was intra-articularly injected into C57BL/6 mice with Hulth surgery-induced osteoarthritis (once a week for 5 consecutive weeks). AM1241 significantly alleviated cartilage degradation and synovial inflammation and suppressed the expression of extracellular matrix degradation markers (MMP-13, ADAMTS-5)[8].
References:
[1] Ibrahim MM, Deng H, Zvonok A, et al. Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10529-33.
[2] Yao BB, Mukherjee S, Fan Y, et al. In vitro pharmacological characterization of AM1241: a protean agonist at the cannabinoid CB2 receptor? Br J Pharmacol. 2006 Sep;149(2):145-54.
[3] Cai Y, Tong F, Li K, et al. Cannabinoid receptor 2 agonist AM1241 alleviates epileptic seizures and epilepsy-associated depression via inhibiting neuroinflammation in a pilocarpine-induced chronic epilepsy mouse model. Mol Cell Neurosci. 2024 Sep;130:103958.
[4] He X, Yang L, Huang R, et al. Activation of CB2R with AM1241 ameliorates neurodegeneration via the Xist/miR-133b-3p/Pitx3 axis. J Cell Physiol. 2020 Sep;235(9):6032-6042.
[5] Sheng B, Wang W, Xia D, et al. Panobinostat (LBH589) combined with AM1241 induces cervical cancer cell apoptosis through autophagy pathway. BMC Pharmacol Toxicol. 2023 Sep 22;24(1):45.
[6] Li S, Yang P, Wu Z, et al. The effects and mechanisms of AM1241 in alleviating cerebral ischemia-reperfusion injury. Brain Res Bull. 2024 Sep;215:111025.
[7] Zhang M, Tian Q, Liu J. Cannabinoid Receptor-2 agonist AM1241 Attenuates Myocardial Ischemia-Reperfusion-Induced Oxidative Stress in Rats via Nrf2/HO-1 Pathway. Med Princ Pract. 2024;33(6):597-606.
[8] Zou Z, Pan S, Sun C, et al. AM1241 inhibits chondrocyte inflammation and ECM degradation through the Nrf2/HO-1 and NF-κB pathways and alleviates osteoarthritis in mice. Mol Med. 2025 Jan 10;31(1):9.
AM1241是一种氨基烷基吲哚类似物，是II型大麻素受体（CB2）的选择性配体，对CB2受体的亲和力（Ki=3.4nM）高于对CB1受体（Ki=280nM）[1-2]。AM1241可用于神经性疼痛和炎症性疼痛的相关研究[3-4]。
在体外，AM1241（4μM）联合LBH589（0.1μM）处理宫颈癌SiHa细胞24小时，AM1241与LBH589协同显著抑制细胞增殖并诱导细胞凋亡，AM1241可激活内质网应激通路、DNA损伤修复信号通路、自噬通路以及增加活性氧（ROS）水平[5]。AM1241（5-20μM）预处理BV2小胶质细胞1小时，随后在H₂O₂（1mM）刺激下培养4小时，AM1241显著抑制H₂O₂诱导的促炎因子TNF-α和IL-6释放、ROS生成以及MD2/TLR4复合物的形成，并减轻细胞凋亡[6]。
在体内，AM1241（6mg/kg）腹腔注射处理心肌缺血再灌注损伤的Sprague-Dawley大鼠（建模前1小时单次给药），AM1241显著改善心功能指标（左心室射血分数和短轴缩短率），降低心肌梗死面积、血清心肌损伤标志物（cTnI、AST、LDH、CK-MB）水平，并减少氧化应激和细胞凋亡 [7]。AM1241（3mg/kg或9mg/kg）关节腔注射处理Hulth手术诱导的骨关节炎C57BL/6小鼠（每周一次，连续5周），AM1241显著减轻软骨降解和滑膜炎症，抑制细胞外基质降解标志物（MMP-13、ADAMTS-5）的表达[8]。