Antinociceptive profile of salvinorin A, a structurally unique kappa opioid receptor agonist

Pharmacol Biochem Behav. 2006 Jan;83(1):109-13. doi: 10.1016/j.pbb.2005.12.011. Epub 2006 Jan 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / antagonists & inhibitors
  • Acetic Acid / toxicity
  • Analgesics*
  • Animals
  • Diterpenes / pharmacology*
  • Diterpenes, Clerodane
  • Dose-Response Relationship, Drug
  • Hot Temperature
  • Male
  • Mice
  • Muscle Contraction / drug effects
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Nociceptors / drug effects
  • Pain Measurement / drug effects
  • Plant Leaves / chemistry
  • Psychotropic Drugs / pharmacology*
  • Reaction Time / drug effects
  • Receptors, Opioid, kappa / agonists*


  • Analgesics
  • Diterpenes
  • Diterpenes, Clerodane
  • Psychotropic Drugs
  • Receptors, Opioid, kappa
  • norbinaltorphimine
  • Naltrexone
  • Acetic Acid
  • salvinorin A