AM-2389 explained

AM-2389 is a classical cannabinoid derivative which acts as a potent and reasonably selective agonist for the CB₁ receptor, with a K_i of 0.16 nM, and 26× selectivity over the related CB₂ receptor. It has high potency in animal tests of cannabinoid activity, and a medium duration of action.^{[1] [2]} Replacing the 1',1'-dimethyl substitution of the dimethylheptyl side chain of classical cannabinoids with cyclopropyl or cyclopentyl results in higher potency than cyclobutyl, but only the cyclobutyl derivatives show selectivity for CB₁ over CB₂.^[3] High selectivity for CB₁ over CB₂ is difficult to achieve (cf. AM-906, AM-1235), as almost all commonly used CB₁ agonists have similar or greater affinity for CB₂ than CB₁, and the only truly highly selective CB₁ agonists known as of 2012 are eicosanoid derivatives such as O-1812.

See also

• HHC
• AMG-36
• AMG-41

Notes and References

1. Nikas SP, Alapafuja SO, Papanastasiou I, Paronis CA, Shukla VG, Papahatjis DP, Bowman AL, Halikhedkar A, Han X, Makriyannis A . 6 . Novel 1',1'-chain substituted hexahydrocannabinols: 9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a highly potent cannabinoid receptor 1 (CB1) agonist . Journal of Medicinal Chemistry . 53 . 19 . 6996–7010 . October 2010 . 20925434 . 10.1021/jm100641g . 3650853 .
2. Järbe TU, Tai S, LeMay BJ, Nikas SP, Shukla VG, Zvonok A, Makriyannis A . AM2389, a high-affinity, in vivo potent CB1-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice . Psychopharmacology . 220 . 2 . 417–26 . March 2012 . 21989802 . 10.1007/s00213-011-2491-1 . 3291515 .
3. Papahatjis DP, Nahmias VR, Nikas SP, Andreou T, Alapafuja SO, Tsotinis A, Guo J, Fan P, Makriyannis A . 6 . C1'-cycloalkyl side chain pharmacophore in tetrahydrocannabinols . Journal of Medicinal Chemistry . 50 . 17 . 4048–60 . August 2007 . 17672444 . 10.1021/jm070121a .