AM-630 explained

AM-630 (6-Iodopravadoline) is a drug that acts as a potent and selective inverse agonist for the cannabinoid receptor CB₂, with a K_i of 32.1 nM at CB₂ and 165x selectivity over CB₁, at which it acted as a weak partial agonist.^{[1] [2]} It is used in the study of CB₂ mediated responses and has been used to investigate the possible role of CB₂ receptors in the brain.^{[3] [4]} AM-630 is significant as one of the first indole derived cannabinoid ligands substituted on the 6-position of the indole ring, a position that has subsequently been found to be important in determining affinity and efficacy at both the CB₁ and CB₂ receptors, and has led to the development of many related derivatives.^{[5] [6] [7] [8] [9]}

See also

• AM-1221
• Pravadoline
• WIN 54,461 (6-Bromopravadoline)

Notes and References

1. Ross RA, Brockie HC, Stevenson LA, Murphy VL, Templeton F, Makriyannis A, Pertwee RG . Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656, and AM630 . British Journal of Pharmacology . 126 . 3 . 665–672 . February 1999 . 10188977 . 1565857 . 10.1038/sj.bjp.0702351 . Alexandros Makriyannis .
2. Murataeva N, Mackie K, Straiker A . The CB2-preferring agonist JWH015 also potently and efficaciously activates CB1 in autaptic hippocampal neurons . Pharmacological Research . 66 . 5 . 437–442 . November 2012 . 22921769 . 3601544 . 10.1016/j.phrs.2012.08.002 .
3. Morgan NH, Stanford IM, Woodhall GL . Functional CB2 type cannabinoid receptors at CNS synapses . Neuropharmacology . 57 . 4 . 356–368 . September 2009 . 19616018 . 10.1016/j.neuropharm.2009.07.017 . 207224823 .
4. Ishiguro H, Horiuchi Y, Ishikawa M, Koga M, Imai K, Suzuki Y, Morikawa M, Inada T, Watanabe Y, Takahashi M, Someya T, Ujike H, Iwata N, Ozaki N, Onaivi ES, Kunugi H, Sasaki T, Itokawa M, Arai M, Niizato K, Iritani S, Naka I, Ohashi J, Kakita A, Takahashi H, Nawa H, Arinami T . 6 . Brain cannabinoid CB2 receptor in schizophrenia . Biological Psychiatry . 67 . 10 . 974–982 . May 2010 . 19931854 . 10.1016/j.biopsych.2009.09.024 . 14222913 .
5. Eissenstat MA, Bell MR, D'Ambra TE, Alexander EJ, Daum SJ, Ackerman JH, Gruett MD, Kumar V, Estep KG, Olefirowicz EM . 6 . Aminoalkylindoles: structure-activity relationships of novel cannabinoid mimetics . Journal of Medicinal Chemistry . 38 . 16 . 3094–3105 . August 1995 . 7636873 . 10.1021/jm00016a013 .
6. https://search.proquest.com/docview/304624325 Hongfeng Deng. Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs. PhD Dissertation, University of Connecticut, 2000.
7. Hynes J, Leftheris K, Wu H, Pandit C, Chen P, Norris DJ, Chen BC, Zhao R, Kiener PA, Chen X, Turk LA, Patil-Koota V, Gillooly KM, Shuster DJ, McIntyre KW . 6 . C-3 Amido-indole cannabinoid receptor modulators . Bioorganic & Medicinal Chemistry Letters . 12 . 17 . 2399–2402 . September 2002 . 12161142 . 10.1016/S0960-894X(02)00466-3 .
8. Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Miller LN, Li L, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD . 6 . Indol-3-yl-tetramethylcyclopropyl ketones: effects of indole ring substitution on CB2 cannabinoid receptor activity . Journal of Medicinal Chemistry . 51 . 6 . 1904–1912 . March 2008 . 18311894 . 10.1021/jm7011613 .
9. Adam, J. M. . Design, synthesis, and structure–activity relationships of indole-3-carboxamides as novel water soluble cannabinoid CB1 receptor agonists . 10.1039/c0md00022a . MedChemComm. 1 . 54 . 2010 . etal.