Muscarinic pain pharmacology: realizing the promise of novel analgesics by overcoming old challenges.
The antinociceptive and analgesic effects of muscarinic receptor ligands in human and nonhuman species have been evident for more than half a century. In this review, we describe the current understanding of the roles of different muscarinic subtypes in pain modulation and their mechanism of action along the pain signaling pathway, including peripheral nociception, spinal cord pain processing, and supraspinal analgesia. Extensive preclinical and clinical validation of these mechanisms points to the development of selective muscarinic agonists as one of the most exciting and promising avenues toward novel pain medications.
Vertex Pharmaceuticals Inc., 11010 Torreyana Road, San Diego, CA 92127, USA. dennis_fiorino@sd.vrtx.com
Dennis F
DF
Fiorino
Miguel
M
Garcia-Guzman
D000109:Acetylcholine / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D008024:Ligands; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000700:Analgesics; D008024:Ligands; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine