Involvement of adenosine A1 and A2A receptors in (-)-linalool-induced antinociception

Life Sci. 2006 Apr 18;78(21):2471-4. doi: 10.1016/j.lfs.2005.10.025. Epub 2005 Dec 15.


In recent studies performed in our laboratory we have shown that acute administration of (-)-linalool, the natural occurring enantiomer in essential oils, possesses anti-inflammatory, antihyperalgesic and antinociceptive effects in different animal models. The antihyperalgesic and antinociceptive effects of (-)-linalool have been ascribed to its capacity in stimulating the opioidergic, cholinergic and dopaminergic systems, as well as to its interaction with K+ channels, or to its local anaesthetic activity and/or to the negative modulation of glutamate transmission. Activation of A1 or A2A receptors has been shown to induce antinociceptive effects, and the possible involvement of adenosine in (-)-linalool antinociceptive effect, has not been elucidated yet. Therefore, in the present study, we have investigated the effects of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A1 receptor antagonist and the effects of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A2A receptor antagonist on the antinociception of (-)-linalool in mice, measured in the hot-plate test. Both DPCPX (0.1 mg/kg; i.p.) and DMPX (0.1 mg/kg; i.p.) pre-treatment significantly depressed the antinociceptive effect of (-)-linalool at the highest doses tested. These findings demonstrated that the effect of (-)-linalool on pain responses is, at least partially, mediated by the activity of adenosine A1 and A2A receptors.

MeSH terms

  • Acyclic Monoterpenes
  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Analgesics*
  • Animals
  • Hot Temperature
  • Male
  • Mice
  • Monoterpenes / pharmacology*
  • Pain Measurement / drug effects
  • Reaction Time / drug effects
  • Receptor, Adenosine A1 / drug effects
  • Receptor, Adenosine A1 / physiology*
  • Receptor, Adenosine A2A / drug effects
  • Receptor, Adenosine A2A / physiology*
  • Theobromine / analogs & derivatives
  • Theobromine / pharmacology
  • Xanthines / pharmacology


  • Acyclic Monoterpenes
  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Analgesics
  • Monoterpenes
  • Receptor, Adenosine A1
  • Receptor, Adenosine A2A
  • Xanthines
  • 3,7-dimethyl-1-propargylxanthine
  • 1,3-dipropyl-8-cyclopentylxanthine
  • linalool
  • Theobromine