AM1241 is a CB(2) receptor-selective agonist. AM1241 displays high affinity at the human CB2 receptor with a Ki value of about 7nM, whereas its affinity at the human CB1 receptor is more than 80-fold weaker. In FLIPR assays, AM1241 exhibits antagonist activity, blocking the agonist CP 55,940-evoked Ca2+ response in a concentration dependent manner with a Kb value of 63nM. The antinociceptive actions of AM1241 are blocked by the CB(2) receptor-selective antagonist AM630, but not by the CB(1) receptor-selective antagonist AM251. AM1241 also produces antinociception when injected systemically (intraperitoneally). [1] AM1241 dose-dependently blocks the agonist activity of CP55,940 (4nM) and the inverse agonist activity of SR144528 (100nM) at the human CB2 receptor with Kb values at 27 and 11nM, respectively.[2]
In vivo
AM1241 dose-dependently reverses tactile and thermal hypersensitivity produces by ligation of the L5 and L6 spinal nerves in rats.AM1241 is also active in blocking spinal nerve ligation-induced tactile and thermal hypersensitivity in mice lacking CB1 receptors (CB1-/- mice).[3] In animal models, AM1241 fully reverses carrageenan-induced inflammatory thermal hyperalgesia when injected into the inflamed paw. AM1241 can also inhibits flinching and thermal hyperalgesia produces by hind paw capsaicin injection.[4] AM1241(33, 330 mg/kg i.p.) can suppresses the development of capsaicin-evoked thermal and mechanical hyperalgesia and allodynia. AM1241 also produces a dose-dependent suppression of capsaicin-evoked nocifensive behavior. AM1241 suppresses capsaicin-evoked hyperalgesia and allodynia through a local site of action.[4]