• Thaiana C F Mendes, Fernanda Antunes, Margarete M Trachez, Nailton M Nascimento, Carlos A M Fraga, Eliezer J Barreiro, Gisele Zapata-Sudo, and Roberto T Sudo.
• Program of Drug Development, Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
• Clin. Exp. Pharmacol. Physiol. 2013 Jul 1; 40 (7): 404-11.

AbstractNew chemicals or adjuvants with analgesic effects on chronic pain are needed and clinically relevant due to the limited number of effective compounds that possess these characteristics. LASSBio-873, a pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivative, activates muscarinic cholinergic receptors and has potent analgesic effects on acute and inflammatory pain. The present study evaluated the therapeutic and prophylactic effects of oral administration of LASSBio-873 in a spinal nerve ligation (SNL) model of chronic peripheral nerve injury. LASSBio-873 (100 mg/kg) inhibited the development of thermal hyperalgesia and mechanical allodynia when administered once daily for 7 consecutive days after SNL surgery and reversed these symptoms. LASSBio-873 treatment did not alter rat behaviour in open field testing measured during the first 24 h after administration and again after 7 continuous days administration. The analgesic effect of LASSBio-873 was inhibited by intrathecal methoctramine, an M2 receptor antagonist, implicating the muscarininc M2 receptor signalling pathway in the drug's action. These results reinforce the potential of LASSBio-873 as a possible prototype for the development of more effective alternatives for the treatment of neuropathic pain.© 2013 Wiley Publishing Asia Pty Ltd.

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