AM-1241

AM-1241
IUPAC ime
	(2-jodo-5-nitrofenil)-[1-[(1-metilpiperidin-2-il)metil]indol-3-il]metanon
Pravni status
Pravni status	Legal;
Identifikatori
CAS broj	444912-48-5
ATC kod	none
PubChem	CID 10141893
ChemSpider	8317404
ChEMBL	CHEMBL408430
Hemijski podaci
Formula	C22H22IN3O3
Molarna masa	503,333 g/mol
	SMILES Ic2ccc(N(=O)=O)cc2C(=O)c(c4ccccc14)cn1CC3CCCCN3C; ;
	InChI 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 ; Key:ZUHIXXCLLBMBDW-UHFFFAOYSA-N ;

AM-1241 (1-(metilpiperidin-2-ilmetil)-3-(2-jodo-5-nitrobenzoil)indol) je jedinjenje iz aminoalkilindolne familije koje deluje kao potentan i selektivan agonist za kanabinoidni receptor CB₂,^[1]^[2] sa K_i od 3,4 nM na CB₂ i 80x selektivnošću u odnosu na srodni CB₁ receptor.^[3]^[4] On ima analgetsko dejstvo u životinjskim studijama, posebno protiv „atipičnog“ bola kao što su hiperalgezija i alodinija.^[5] Smatra se da je to dejstvo posredovano putem CB₂ perifernog otpuštanja endogenih opioidnih peptida,^[6] kao i direktne aktivacije TRPA1 kanala.^[7] On je takođe pokazao efikasnost u tretmanu amiotrofične lateralne skleroze u životinjskim modelima.^[8]^[9]

Reference

^ Yao BB, Mukherjee S, Fan Y, Garrison TR, Daza AV, Grayson GK, Hooker BA, Dart MJ, Sullivan JP, Meyer MD (2006). „In vitro pharmacological characterization of AM1241: a protean agonist at the cannabinoid CB2 receptor?”. British Journal of Pharmacology. 149 (2): 145—54. PMC 2013801 . PMID 16894349. doi:10.1038/sj.bjp.0706838.
^ Bingham B, Jones PG, Uveges AJ, Kotnis S, Lu P, Smith VA, Sun SC, Resnick L, Chlenov M, He Y, Strassle BW, Cummons TA, Piesla MJ, Harrison JE, Whiteside GT, Kennedy JD (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 2042933 . PMID 17549048. doi:10.1038/sj.bjp.0707303.
^ Ibrahim MM, Deng H, Zvonok A, Cockayne DA, Kwan J, Mata HP, Vanderah TW, Lai J, Porreca F, Makriyannis A, Malan TP (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 193595 . PMID 12917492. doi:10.1073/pnas.1834309100.
^ 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.
^ Beltramo M, Bernardini N, Bertorelli R, Campanella M, Nicolussi E, Fredduzzi S, Reggiani A (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.
^ Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, Davar G, Makriyannis A, Vanderah TW, Mata HP, Malan TP (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 549497 . PMID 15705714. doi:10.1073/pnas.0409888102.
^ Akopian AN, Ruparel NB, Patwardhan A, Hargreaves KM (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.
^ Kim K, Moore DH, Makriyannis A, Abood ME (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.
^ Shoemaker JL, Seely KA, Reed RL, Crow JP, Prather PL (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 2819701 . PMID 17241118. doi:10.1111/j.1471-4159.2006.04346.x.

Vidi još

[pmid16894349-1] Yao BB, Mukherjee S, Fan Y, Garrison TR, Daza AV, Grayson GK, Hooker BA, Dart MJ, Sullivan JP, Meyer MD (2006). „In vitro pharmacological characterization of AM1241: a protean agonist at the cannabinoid CB2 receptor?”. British Journal of Pharmacology. 149 (2): 145—54. PMC 2013801 . PMID 16894349. doi:10.1038/sj.bjp.0706838.

[pmid17549048-2] Bingham B, Jones PG, Uveges AJ, Kotnis S, Lu P, Smith VA, Sun SC, Resnick L, Chlenov M, He Y, Strassle BW, Cummons TA, Piesla MJ, Harrison JE, Whiteside GT, Kennedy JD (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 2042933 . PMID 17549048. doi:10.1038/sj.bjp.0707303.

[pmid12917492-3] Ibrahim MM, Deng H, Zvonok A, Cockayne DA, Kwan J, Mata HP, Vanderah TW, Lai J, Porreca F, Makriyannis A, Malan TP (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 193595 . PMID 12917492. doi:10.1073/pnas.1834309100.

[pmid18289088-4] 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.

[pmid16553616-5] Beltramo M, Bernardini N, Bertorelli R, Campanella M, Nicolussi E, Fredduzzi S, Reggiani A (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.

[pmid15705714-6] Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, Davar G, Makriyannis A, Vanderah TW, Mata HP, Malan TP (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 549497 . PMID 15705714. doi:10.1073/pnas.0409888102.

[pmid18234885-7] Akopian AN, Ruparel NB, Patwardhan A, Hargreaves KM (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.

[pmid16781706-8] Kim K, Moore DH, Makriyannis A, Abood ME (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.

[pmid17241118-9] Shoemaker JL, Seely KA, Reed RL, Crow JP, Prather PL (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 2819701 . PMID 17241118. doi:10.1111/j.1471-4159.2006.04346.x.

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