AM-1241
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| Systematic (IUPAC) name | |
| (2-iodo-5-nitrophenyl)-[1-[(1-methylpiperidin-2-yl)methyl]indol-3-yl]methanone | |
| Clinical data | |
| Pregnancy cat. | ? |
| Legal status | Legal |
| Identifiers | |
| CAS number | 444912-48-5  |
| ATC code | ? |
| PubChem | CID 10141893 |
| ChemSpider | 8317404 |
| ChEMBL | CHEMBL408430 |
| Chemical data | |
| Formula | C22H22IN3O3 |
| Mol. mass | 503.333 g/mol |
| SMILES | eMolecules & PubChem |
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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,[1][2] with a Ki of 3.4nM at CB2 and 80x 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 endogeous 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]
[edit] 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]
[edit] See also
[edit] References
- ^ Yao BB, Mukherjee S, Fan Y, Garrison TR, Daza AV, Grayson GK, Hooker BA, Dart MJ, Sullivan JP, Meyer MD (September 2006). "In vitro pharmacological characterization of AM1241: a protean agonist at the cannabinoid CB2 receptor?". British Journal of Pharmacology 149 (2): 145–54. doi:10.1038/sj.bjp.0706838. PMC 2013801. PMID 16894349. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2013801.
- ^ Bingham B, Jones PG, Uveges AJ, Kotnis S, Lu P, Smith VA, Sun SC, Resnick L, Chlenov M, He Y, Strassle BW, Cummons TA, Piesla MJ, Harrison JE, Whiteside GT, Kennedy JD (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2042933.
- ^ Ibrahim MM, Deng H, Zvonok A, Cockayne DA, Kwan J, Mata HP, Vanderah TW, Lai J, Porreca F, Makriyannis A, Malan TP (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=193595.
- ^ 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. PMID 18289088.
- ^ 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. PMID 16553616.
- ^ Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, Davar G, Makriyannis A, Vanderah TW, Mata HP, Malan TP (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=549497.
- ^ Akopian AN, Ruparel NB, Patwardhan A, Hargreaves KM (January 2008). "Cannabinoids desensitize capsaicin and mustard oil responses in sensory neurons via TRPA1 activation". Journal of Neuroscience 28 (5): 1064–75. doi:10.1523/JNEUROSCI.1565-06.2008. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2819701.
- ^ Lozano, Alysia (April 2010). "A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss". Life Sciences: 646–53. PMID 20176037.
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