LY2828360

LY2828360 is a slowly acting but efficacious G protein-biased cannabinoid (CB₂) agonist, inhibiting cAMP accumulation and activating ERK1/2 signaling. IC50 & Target: CB₂^[1]. 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].