AM-1241

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
CompTox Dashboard (EPA)
ECHA InfoCard100.164.689 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]

  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.