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

• Published in: Pharmacology, biochemistry and behavior Vol. 83; no. 1; pp. 109 - 113
• Main Authors: McCurdy, Christopher R., Sufka, Kenneth J., Smith, Grant H., Warnick, Jason E., Nieto, Marcelo J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2006; Elsevier Science
• Subjects: Acetic Acid - antagonists & inhibitors; Acetic Acid - toxicity; Acetic acid writhing; Analgesics; Animals; Antinociception; Biological and medical sciences; Diterpenes - pharmacology; Diterpenes, Clerodane; Dose-Response Relationship, Drug; Hot Temperature; Hotplate; Kappa opioid receptor agonist; Male; Medical sciences; Mice; Mouse; 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; Salvinorin A; Tail-flick; Acetic acid writhing; Kappa opioid receptor agonist; Tail-flick; Mouse; Salvinorin A; Antinociception; Hotplate; Agonist; Rodentia; κ Opioid receptor; Analgesia; Vertebrata; Mammalia; Analgesic; Animal; Acetic acid
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2005.12.011

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.