Kavain analogues as potential analgesic agents

Pharmacol Rep. 2012;64(6):1419-26. doi: 10.1016/s1734-1140(12)70939-8.

Abstract

Background: Kavalactones are pharmacologically active compounds present in preparations of the root trunk of Piper methysticum Forst, known as kava. This work describes the analgesic activity of some synthesized analogues of synthetic kavain, which is the main component of kava.

Methods: The essays were initially performed against the writhing test in mice, and the most promising compound was analyzed using other classical models of nociception, including formalin-, capsaicin-, glutamate-induced nociception, the hot plate test, and measurement of motor performance.

Results: The results indicated that compound 6-(4-fluorophenyl)-4-methoxy-5,6-dihydropyran-2-one (2d) exerts potent and dose-dependent analgesic activity, inhibiting abdominal constrictions caused by acetic acid in mice, and being more active than some reference drugs. It also presented activity in the other models of pain, with the exception of the hot plate test and the measurement of motor performance.

Conclusions: Although compound 2d exerts antinociceptive activity, the mechanism of action remains uncertain, but it does not involve the opioid system and does not appear to be associated with non-specific effects such as changes in locomotor activity or motor coordination.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Molecular Structure
  • Motor Activity / drug effects
  • Pain / etiology
  • Pain / physiopathology
  • Pain / prevention & control*
  • Pain / psychology
  • Pain Measurement
  • Pain Threshold / drug effects*
  • Psychomotor Performance / drug effects
  • Pyrones / chemical synthesis
  • Pyrones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Pyrones
  • kavain