AM-1241

AM-1241
Systematic (IUPAC) name
(2-iodo-5-nitrophenyl)-[1-[(1-methylpiperidin-2-yl)methyl]indol-3-yl]methanone
Clinical data
Legal status
Identifiers
CAS Number 444912-48-5 N
PubChem CID 10141893
IUPHAR/BPS 3316
ChemSpider 8317404 YesY
ChEMBL CHEMBL408430 YesY
Chemical data
Formula C22H22IN3O3
Molar mass 503.333 g/mol
 NYesY (what is this?)  (verify)

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]

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]

See also

References

  1. ↑ Yao BB; et al. (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.
  2. ↑ Bingham B; 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.
  3. ↑ Ibrahim MM; 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.
  4. ↑ 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.
  5. ↑ Beltramo M; et al. (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.
  6. ↑ Ibrahim MM; 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Shoemaker JL; et al. (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.
  10. ↑ Lozano, Alysia (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. Retrieved 18 December 2011.


This article is issued from Wikipedia - version of the Friday, February 05, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.