A-425619 [1-Isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a Novel Transient Receptor Potential Type V1 Receptor Antagonist, Relieves Pathophysiological Pain Associated with Inflammation and Tissue Injury in Rats
| Autor: | Chengmin Zhong, Donna M. Gauvin, Arthur Gomtsyan, Prisca Honore, Connie R. Faltynek, James P. Sullivan, Rachid El Kouhen, Chang Z. Zhu, Joseph P. Mikusa, Michael F. Jarvis, Kennan C. Marsh, Carol T. Wismer, Chih-Hung Lee |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Hot Temperature Receptors Drug Freund's Adjuvant TRPV1 Pain Inflammation Motor Activity Pharmacology Carrageenan Rats Sprague-Dawley chemistry.chemical_compound Formaldehyde Osteoarthritis medicine Animals Edema Urea Receptor Ligation Postural Balance Pain Measurement Analgesics Pain Postoperative Dose-Response Relationship Drug business.industry Antagonist Isoquinolines Sciatic Nerve Rats Spinal Nerves Nociception chemistry Hyperalgesia Capsaicin Freund's adjuvant Acute Disease Chronic Disease Neuropathic pain Molecular Medicine medicine.symptom business |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 314:410-421 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.105.083915 |
| Popis: | The vanilloid receptor 1 (VR1, TRPV1), which is a member of the transient receptor potential (TRP) superfamily, is highly localized on peripheral and central processes of nociceptive afferent fibers. Activation of TRPV1 contributes to the pronociceptive effects of capsaicin, protons, heat, and various endogenous lipid agonists such as anandamide and N-arachidonoyl-dopamine. A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)urea] is a novel potent and selective antagonist at both human and rat TRPV1 receptors. In vivo, A-425619 dose dependently reduced capsaicin-induced mechanical hyperalgesia (ED50 = 45 micromol/kg p.o.). A-425619 was also effective in models of inflammatory pain and postoperative pain. A-425619 potently reduced complete Freund's adjuvant-induced chronic inflammatory pain after oral administration (ED50 = 40 micromol/kg p.o.) and was also effective after either i.t. administration or local injection into the inflamed paw. Furthermore, A-425619 maintained efficacy in the postoperative pain model after twice daily dosing p.o. for 5 days. A-425619 also showed partial efficacy in models of neuropathic pain. A-425619 did not alter motor performance at the highest dose tested (300 micromol/kg p.o.). Taken together, the present data indicate that A-425619, a potent and selective antagonist of TRPV1 receptors, effectively relieves acute and chronic inflammatory pain and postoperative pain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|