Antihyperalgesic effects of a novel muscarinic agonist (LASSBio-873) in spinal nerve ligation in rats

作者：Mendes Thaiana C F; Antunes Fernanda; Trachez Margarete M; Nascimento Nailton M Jr; Fraga Carlos A M; Barreiro Eliezer J; Zapata Sudo Gisele^*; Sudo Roberto T

来源：Clinical and Experimental Pharmacology and Physiology, 2013, 40(7): 404-411.

DOI：10.1111/1440-1681.12090

• Pyrazolo[3
• 4-b]pyrrolo[3
• 4-d]pyridine derivatives
• chronic pain
• hyperalgesia
• muscarinic
• spinal nerve ligation

New 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 (100mg/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 24h 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%26apos;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.

• 出版日期2013-7