Effects of imidazoline I ₂ receptor ligands on acute nociception in rats

This study examined the antinociceptive effects of seven imidazoline I ₂ receptor ligands in a rat warm water tail withdrawal procedure (46 and 50°C). Agmatine, 2-BFI, phenyzoline, and diphenyzoline produced a significant antinociceptive activity at 46°C. BU224, S22687, and idazoxan had no effect at 46°C up to doses that altered the locomotor activity. None of the drugs showed antinociceptive activity at 50°C. It is suggested that I ₂ receptor agonists have antinociceptive activity for acute phasic pain under weak noxious stimulus, and the effects are efficacy-dependent. These data explain the findings that I ₂ receptor agonists enhance the antinociceptive effects of opioids and support developing higher-efficacy I ₂ receptor agonists for the treatment of pain.