AM-1241

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AM-1241
AM-1241-2D-skeletal.svg
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
ChEMBL
ECHA InfoCard 100.164.689
Chemical and physical data
Formula C22H22IN3O3
Molar mass 503.333 g/mol
3D model (JSmol)
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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]

Effects in bone cancer model[edit]

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[edit]

References[edit]

  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. PMC 2013801Freely accessible. PMID 16894349. doi:10.1038/sj.bjp.0706838. 
  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. PMC 2042933Freely accessible. PMID 17549048. doi:10.1038/sj.bjp.0707303. 
  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. PMC 193595Freely accessible. PMID 12917492. doi:10.1073/pnas.1834309100. 
  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. PMID 18289088. doi:10.2174/156802608783498014. 
  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. PMID 16553616. doi:10.1111/j.1460-9568.2006.04684.x. 
  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. PMC 549497Freely accessible. PMID 15705714. doi:10.1073/pnas.0409888102. 
  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. PMID 18234885. doi:10.1523/JNEUROSCI.1565-06.2008. 
  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. PMID 16781706. doi:10.1016/j.ejphar.2006.05.025. 
  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. PMC 2819701Freely accessible. PMID 17241118. doi:10.1111/j.1471-4159.2006.04346.x. 
  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. PMC 2871326Freely accessible. PMID 20176037. doi:10.1016/j.lfs.2010.02.014.