Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-6-20
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
410-21
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15837818-Acute Disease, pubmed-meshheading:15837818-Analgesics, pubmed-meshheading:15837818-Animals, pubmed-meshheading:15837818-Capsaicin, pubmed-meshheading:15837818-Carrageenan, pubmed-meshheading:15837818-Chronic Disease, pubmed-meshheading:15837818-Dose-Response Relationship, Drug, pubmed-meshheading:15837818-Edema, pubmed-meshheading:15837818-Formaldehyde, pubmed-meshheading:15837818-Freund's Adjuvant, pubmed-meshheading:15837818-Hot Temperature, pubmed-meshheading:15837818-Hyperalgesia, pubmed-meshheading:15837818-Inflammation, pubmed-meshheading:15837818-Isoquinolines, pubmed-meshheading:15837818-Ligation, pubmed-meshheading:15837818-Male, pubmed-meshheading:15837818-Motor Activity, pubmed-meshheading:15837818-Osteoarthritis, pubmed-meshheading:15837818-Pain, pubmed-meshheading:15837818-Pain, Postoperative, pubmed-meshheading:15837818-Pain Measurement, pubmed-meshheading:15837818-Postural Balance, pubmed-meshheading:15837818-Rats, pubmed-meshheading:15837818-Rats, Sprague-Dawley, pubmed-meshheading:15837818-Receptors, Drug, pubmed-meshheading:15837818-Sciatic Nerve, pubmed-meshheading:15837818-Spinal Nerves, pubmed-meshheading:15837818-Urea
pubmed:year
2005
pubmed:articleTitle
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.
pubmed:affiliation
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. marie.honore@abbott.com
pubmed:publicationType
Journal Article