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

Summary 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 receptor...

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Published in:	Clinical and experimental pharmacology & physiology Vol. 40; no. 7; pp. 404 - 411
Main Authors:	Mendes, Thaiana CF, Antunes, Fernanda, Trachez, Margarete M, Nascimento Jr, Nailton M, Fraga, Carlos AM, Barreiro, Eliezer J, Zapata-Sudo, Gisele, Sudo, Roberto T
Format:	Journal Article
Language:	English
Published:	Australia Blackwell Publishing Ltd 01-07-2013 Wiley Subscription Services, Inc
Subjects:	4-b]pyrrolo 4-d]pyridine derivatives Analgesics - pharmacology Animals chronic pain hyperalgesia Hyperalgesia - drug therapy Hyperalgesia - metabolism Male muscarinic Muscarinic Agonists - pharmacology Neuralgia - drug therapy Neuralgia - metabolism Pain Measurement - methods Peripheral Nerve Injuries - drug therapy Peripheral Nerve Injuries - metabolism Pyrazoles - pharmacology Pyrazolo Pyrazolo[3,4‐b]pyrrolo[3,4‐d]pyridine derivatives Pyridines - pharmacology Pyrroles - pharmacology Rats Rats, Wistar Receptor, Muscarinic M2 - antagonists & inhibitors Receptor, Muscarinic M2 - metabolism spinal nerve ligation Spinal Nerves - drug effects Spinal Nerves - metabolism
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Summary:	Summary 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.
Bibliography:	ArticleID:CEP12090 ark:/67375/WNG-672TT7M8-8 istex:D8778FB14611DE48B6DB3AC13B94D69772D0A270 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0305-1870 1440-1681
DOI:	10.1111/1440-1681.12090