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AM-1241
Legal status
Legal status
Identifiers
  • (2-Iodo-5-nitrophenyl)-[1-[(1-methylpiperidin-2-yl)methyl]indol-3-yl]methanone
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
ECHA InfoCard 100.164.689 Edit this at Wikidata
Chemical and physical data
FormulaC22H22IN3O3
Molar mass503.340 g·mol−1
3D model ( JSmol)
  • Ic2ccc(N(=O)=O)cc2C(=O)c(c4ccccc14)cn1CC3CCCCN3C
  • InChI=1S/C22H22IN3O3/c1-24-11-5-4-6-16(24)13-25-14-19(17-7-2-3-8-21(17)25)22(27)18-12-15(26(28)29)9-10-20(18)23/h2-3,7-10,12,14,16H,4-6,11,13H2,1H3 checkY
  • Key:ZUHIXXCLLBMBDW-UHFFFAOYSA-N checkY
 ☒NcheckY  (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 3.4 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]

See also

References

  1. ^ Yao BB, Mukherjee S, Fan Y, Garrison TR, Daza AV, Grayson GK, 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, 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.
  3. ^ 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. Bibcode: 2003PNAS..10010529I. 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, 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. S2CID  19266396.
  6. ^ 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. Bibcode: 2005PNAS..102.3093I. 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". The Journal of Neuroscience. 28 (5): 1064–75. doi: 10.1523/JNEUROSCI.1565-06.2008. PMC  6671418. 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, 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.
  10. ^ 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.
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