title: Antihyperalgesic effects of a novel muscarinic agonist (LASSBio-873) in spinal nerve ligation in rats.
abstract: 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 (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.
authors.affiliation: Program of Drug Development, Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Thaiana C F
authors.initials: TC
authors.lastname: Mendes
authors.forename: Fernanda
authors.initials: F
authors.lastname: Antunes
authors.forename: Margarete M
authors.initials: MM
authors.lastname: Trachez
authors.forename: Nailton M
authors.initials: NM
authors.lastname: Nascimento
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Gisele
authors.initials: G
authors.lastname: Zapata-Sudo
authors.forename: Roberto T
authors.initials: RT
authors.lastname: Sudo
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D059348:Peripheral Nerve Injuries / Q000188:drug therapy* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013127:Spinal Nerves / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000700:Analgesics; C545612:LASSBio-873; D018721:Muscarinic Agonists; D011720:Pyrazoles; D011725:Pyridines; D011758:Pyrroles; D043585:Receptor, Muscarinic M2