Novel series of CB2 selective agonists for the treatment of neuropathic pain

PETROV, R.R.; ASTRUC-DIAZ, FANNY; CAVASOTTO, CLAUDIO N.; DIAZ, PHILIPPE

Anaheim, CA

Conferencia; 241st Meeting of the American Chemical Society; 2011

Neuropathic pain is among the most challenging types of chronic pain to treat, resulting in 8% of people worldwide with a "burning" or "electrical" pain. With the exact disease mechanisms still poorly elucidated, the most common causes of neuropathic pain include diabetes, nerve injury, exposure to toxins, and inadequate blood supply. Conventional painkillers have been poorly effective in treating neuropathic pain, which is refractory to traditional analgesia. The cannabinoid receptor CB2, has emerged as a new target for the treatment of inflammatory disorders, without the CB1 mediated psychotropic side effects. We sought to develop selective CB2 agonists and assess their potency. Novel cannabinoid modulators based on a tricyclic scaffold, have been prepared. Selected compounds were tested on in vivo relevant models of neuropathic pain with the goal of reversing allodynia and hyperalgesia. We will report details of the synthesis, in vitro characterization, molecular modeling and in vivo testing of the new analogues.