AM-1241 (1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole) is a chemical from the aminoalkylindole family that acts as a potent and selective agonist for the cannabinoid receptorCB2,[1][2] with a Ki of 3.4 nM at CB2 and 80 times selectivity over the related CB1 receptor.[3][4] It has analgesic effects in animal studies, particularly against "atypical" pain such as hyperalgesia and allodynia.[5] This is thought to be mediated through CB2-mediated peripheral release of endogenous opioid peptides,[6] as well as direct activation of the TRPA1 channel.[7] It has also shown efficacy in the treatment of amyotrophic lateral sclerosis in animal models.[8][9]
Effects in bone cancer model
The antihyperalgesic effects of AM-1241 were investigated in a murine bone cancer model. Sarcoma cells were injected into the femur of a mouse, and then mice were injected twice daily with AM-1241. Treatment with AM-1241 reduced both spontaneous and evoked pain, as well as reducing the bone loss and subsequent fractures due to the tumor. Pretreatment with the CB2 antagonist SR-144,528 reversed the acute effects of AM-1241 on both spontaneous and evoked pain, while having no effect on its own.[10]
^Marriott KS, Huffman JW (2008). "Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor". Current Topics in Medicinal Chemistry. 8 (3): 187–204. doi:10.2174/156802608783498014. PMID18289088.
^Beltramo M, Bernardini N, Bertorelli R, Campanella M, Nicolussi E, Fredduzzi S, Reggiani A (March 2006). "CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms". The European Journal of Neuroscience. 23 (6): 1530–8. doi:10.1111/j.1460-9568.2006.04684.x. PMID16553616. S2CID19266396.
^Kim K, Moore DH, Makriyannis A, Abood ME (August 2006). "AM1241, a cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis". European Journal of Pharmacology. 542 (1–3): 100–5. doi:10.1016/j.ejphar.2006.05.025. PMID16781706.
