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This study examined the antinociceptive effects of seven imidazoline I(2) receptor ligands in a rat warm water tail withdrawal procedure (46 and 50 degrees C). Agmatine, 2-BFI, phenyzoline, and diphenyzoline produced a significant antinociceptive activity at 46 degrees C. BU224, S22687, and idazoxan had no effect at 46 degrees C up to doses that altered the locomotor activity. None of the drugs showed antinociceptive activity at 50 degrees 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. NeuroReport 23:73-77 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
