SYNTHESIS AND ANTIALLODYNIC ACTIVITY OF CANNABIDIOL ANALOGUE ON PERIPHERAL NEUROPATHY IN MICE.

Cannabidiol (CBD) is a substance that exerts several therapeutic actions, including analgesia. CBD is generally administered orally, but its poor water solubility and metabolism impairs its bioavailability. Thus, the development of molecules with better pharmacokinetic profile from cannabidiol becomes an interesting strategy for the design of novel analgesic drugs for the relief of painful conditions that are difficult to manage clinically, such as neuropathic pain. In the present study, an unprecedented analogue of CBD (1) was synthesized and some of its physicochemical properties were evaluated in silico as well as its stability in an acid medium. Additionally, its effect was investigated in a model of neuropathic pain induced by the chemotherapy drug paclitaxel in mice, in comparison with cannabidiol itself. Cannabidiol (20 mg/kg), pregabalin (30 mg/kg) or analogue 1 (5, 10 and 20 mg/kg), administered on the fourteenth day after the first administration of paclitaxel, attenuated the mechanical allodynia of the sensitized animals. The antinociceptive activity of the 1 was attenuated by previous administration of a cannabinoid CB1 receptor antagonist, AM 251, which indicates that its mechanism of action is related to the activation of CB1 receptors.