Uses
LY2828360 is a slowly acting but efficacious G protein-biased cannabinoid (CB2) agonist, inhibiting cAMP accumulation and activating ERK1/2 signaling.
Biological Activity
LY2828360 is a potent and selective slowly acting G protein-biased CB2 cannabinoid agonist th at inhibits cAMP accumulation and activates ERK1/2 signaling while failing to recruit arrestin. LY2828360 suppress chemotherapy-induced neuropathic pain created by paclitaxel without producing tolerance in mice.
in vivo
In WT mice, acute systemic administration of LY2828360 suppresses paclitaxel-induced mechanical and cold allodynia in a dose-dependent manner. LY2828360 produces time-dependent suppressions of paclitaxel-evoked mechanical and cold hypersensitivities and suppression of allodynia is maintained for at least 4.5 h post-injection relative to drug pre-injection levels. At 24 h post-injection, paclitaxel-induced mechanical allodynia has returned to drug pre-injection levels of hypersensitivity. Residual suppression of cold allodynia was absent by 72 h post LY2828360 treatment. Previously chronic administration of LY2828360 blocks the development of tolerance to the antiallodynic effects of morphine in WT but not in CB2KO mice. Chronic LY2828360 treatment suppresses paclitaxel-induced mechanical and cold allodynia in WT mice but not in CB2KO mice previously render tolerant to morphine[1].
References
[1] Lin X, et al. Slowly Signaling G Protein-Biased CB2 Cannabinoid Receptor Agonist LY2828360 Suppresses Neuropathic Pain with Sustained Efficacy and Attenuates Morphine Tolerance and Dependence. Mol Pharmacol. 2018 Feb;93(2):49-62. DOI:
10.1124/mol.117.109355
