World Library  
Flag as Inappropriate
Email this Article


Article Id: WHEBN0014758056
Reproduction Date:

Title: Pravadoline  
Author: World Heritage Encyclopedia
Language: English
Subject: Indometacin, Benzydamine
Publisher: World Heritage Encyclopedia


Pravadoline (WIN 48,098) is an antiinflammatory and analgesic drug with an IC50 of 4.9 µM, related in structure to non-steroidal antinflammtory drugs (NSAIDs) such as indometacin. It was developed in the 1980s as a new antiinflammatory and prostaglandin synthesis inhibitor, acting through inhibition of the enzyme cyclooxygenase (COX).

However, pravadoline was found to exhibit unexpectedly strong analgesic effects, which appeared at doses ten times smaller than the effective anti-inflammatory dose and so could not be explained by its action as a COX inhibitor. These effects were not blocked by opioid antagonists such as naloxone,[1] and it was eventually discovered that pravadoline represented the first compound from a novel class of cannabinoid agonists, the aminoalkylindoles.[2]

Pravadoline was never developed for use as an analgesic, partly due to toxicity concerns (although these were later shown to be a result of the salt form that the drug had been prepared in rather than from the pravadoline itself),[3] however the discovery of cannabinoid activity in this structurally novel family of drugs led to the discovery of several new cannabinoid agonists, including the drug WIN 55,212-2, which is now widely used in scientific research.[4][5]

Animal studies

Administration of pravadoline on rats showed:[1]

  • Prolonged the response latency induced by tail immersion in hot water at a temperature of 55 degrees Celsius (minimum effective dose, 100mg/kg s.c.)
  • Prevented hyperalgesia in rats with Brewer's Yeast injections during (Randall-Selitto test) (minimum effective dose, 1mg/kg, p.o.)
  • Prevented the nociceptive response induced by paw flexion in the adjuvant-arthritic rat (ED50,41mg/kg, p.o.)
  • Prevented the nociceptive response of bradykinin-induced head and forepaw flexion (ED50, 78mg/kg, p.o.)

The antinociceptive activity of pravadoline cannot be explained by an opioid mechanism, because pravadoline-induced antinociception was not antagonized by naloxone (1mg/kg, s.c.) and pravadoline did not bind to the opioid receptors at concentrations up to 10μM.[1]

See also

  • AM-630 (6-iodopravadoline)
  • WIN 54,461 (6-bromopravadoline)
  • WIN 55,212-2
  • RCS-4 (1-pentyl-3-(4-methoxybenzoyl)indole)


This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.