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AM-1241

January 01, 1970

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]

AM-1241
Legal status
Legal status
Identifiers
  • (2-Iodo-5-nitrophenyl)-[1-[(1-methylpiperidin-2-yl)methyl]indol-3-yl]methanone
CAS Number
  • 444912-48-5 N
PubChem CID
  • 10141893
IUPHAR/BPS
  • 3316
ChemSpider
  • 8317404 Y
UNII
  • DLM851L3RD
ChEMBL
  • ChEMBL408430 Y
CompTox Dashboard (EPA)
  • DTXSID301017015
ECHA InfoCard100.164.689
Chemical and physical data
FormulaC22H22IN3O3
Molar mass503.340 g·mol−1
3D model (JSmol)
  • Interactive image
  • 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 Y
  • Key:ZUHIXXCLLBMBDW-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

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, 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.

January 01, 1970
1241, methylpiperidin, ylmethyl, iodo, nitrobenzoyl, indole, chemical, from, aminoalkylindole, family, that, acts, potent, selective, agonist, cannabinoid, receptor, with, times, selectivity, over, related, receptor, analgesic, effects, animal, studies, partic. 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 AM 1241Legal statusLegal statusCA Schedule II DE NpSG Industrial and scientific use only UK Under Psychoactive Substances ActIdentifiersIUPAC name 2 Iodo 5 nitrophenyl 1 1 methylpiperidin 2 yl methyl indol 3 yl methanoneCAS Number444912 48 5 NPubChem CID10141893IUPHAR BPS3316ChemSpider8317404 YUNIIDLM851L3RDChEMBLChEMBL408430 YCompTox Dashboard EPA DTXSID301017015ECHA InfoCard100 164 689Chemical and physical dataFormulaC 22H 22I N 3O 3Molar mass503 340 g mol 13D model JSmol Interactive imageSMILES Ic2ccc N O O cc2C O c c4ccccc14 cn1CC3CCCCN3CInChI 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 YKey ZUHIXXCLLBMBDW UHFFFAOYSA N Y N Y what is this verify Effects in bone cancer model editThe 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 editAM 1220 AM 1248 AM 2233References edit 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 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 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 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 S2CID 19266396 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 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 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 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 Retrieved from https en wikipedia org w index php title AM 1241 amp oldid 1194226196, wikipedia, wiki, book, books, library,

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