Antinociceptive profile of salvinorin A, a structurally unique kappa opioid receptor agonist.
Salvinorin A, is a structurally unique, non-nitrogenous, kappa opioid receptor (KOP) agonist. Given the role of KOPs in analgesic processes, we set out to determine whether salvinorin A has antinociceptive activity in thermal and chemo-nociceptive assays. The tail-flick assay was employed to investigate 1) salvinorin A's (0.5, 1.0, 2.0, and 4.0 mg/kg) dose-response and time-course (10, 20, and 30 min) effects in a thermal nociceptive assay, and 2) the ability for the KOP antagonist norBNI (10.0 mg/kg) to prevent salvinorin A antinociception. The hotplate assay was utilized as a second thermal nociceptive measure to test salvinorin A's dose-response effects. The acetic acid abdominal constriction assay was used to study salvinorin A's dose-response and time-course (over 30 min) effects in a chemo-nociceptive assay. Together, these studies revealed that salvinorin A produces a dose-dependent antinociception that peaked at 10 min post-injection but rapidly returned to baseline. Additionally, pretreatment with the KOP antagonist norbinaltorphimine (norBNI) reversed salvinorin A-induced antinociception. These findings demonstrate that salvinorin A produces a KOP mediated antinociceptive effect with a short duration of action.
McCurdy
Christopher R
CR
Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, University, MS 38677, USA. cmccurdy@olemiss.edu
Sufka
Kenneth J
KJ
Smith
Grant H
GH
Warnick
Jason E
JE
Nieto
Marcelo J
MJ
D019342:Acetic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D000700:Analgesics; D000818:Animals; D004224:Diterpenes / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D018515:Plant Leaves / Q000737:chemistry; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D000700:Analgesics; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D011619:Psychotropic Drugs; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019342:Acetic Acid; C090499:salvinorin A