|Chemical and physical data|
|Molar mass||503.340 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
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 receptor CB2, with a Ki of 3.4 nM at CB2 and 80 times selectivity over the related CB1 receptor. It has analgesic effects in animal studies, particularly against "atypical" pain such as hyperalgesia and allodynia. This is thought to be mediated through CB2-mediated peripheral release of endogenous opioid peptides, as well as direct activation of the TRPA1 channel. It has also shown efficacy in the treatment of amyotrophic lateral sclerosis in animal models.
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.
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- Bingham B, Jones PG, Uveges AJ, Kotnis S, Lu P, Smith VA, et al. (August 2007). "Species-specific in vitro pharmacological effects of the cannabinoid receptor 2 (CB2) selective ligand AM1241 and its resolved enantiomers". British Journal of Pharmacology. 151 (7): 1061–70. doi:10.1038/sj.bjp.0707303. PMC 2042933. PMID 17549048.
- Ibrahim MM, Deng H, Zvonok A, Cockayne DA, Kwan J, Mata HP, et al. (September 2003). "Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS". Proceedings of the National Academy of Sciences of the United States of America. 100 (18): 10529–33. doi:10.1073/pnas.1834309100. PMC 193595. PMID 12917492.
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- Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, et al. (February 2005). "CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids". Proceedings of the National Academy of Sciences of the United States of America. 102 (8): 3093–8. doi:10.1073/pnas.0409888102. PMC 549497. PMID 15705714.
- Akopian AN, Ruparel NB, Patwardhan A, Hargreaves KM (January 2008). "Cannabinoids desensitize capsaicin and mustard oil responses in sensory neurons via TRPA1 activation". The Journal of Neuroscience. 28 (5): 1064–75. doi:10.1523/JNEUROSCI.1565-06.2008. PMC 6671418. PMID 18234885.
- 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. PMID 16781706.
- Shoemaker JL, Seely KA, Reed RL, Crow JP, Prather PL (April 2007). "The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset". Journal of Neurochemistry. 101 (1): 87–98. doi:10.1111/j.1471-4159.2006.04346.x. PMC 2819701. PMID 17241118.
- Lozano-Ondoua AN, Wright C, Vardanyan A, King T, Largent-Milnes TM, Nelson M, et al. (April 2010). "A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss". Life Sciences. 86 (17–18): 646–53. doi:10.1016/j.lfs.2010.02.014. PMC 2871326. PMID 20176037.