Effects of imidazoline I₂ receptor ligands on morphine- and tramadol-induced antinociception in rats
2011
Thorn, David A. | Zhang, Yanan | Peng, Bi-Wen | Winter, Jerrold C. | Li, Jun-Xu
Currently available analgesics cannot meet the increasing clinical needs and new analgesics with better therapeutic profiles are in great demand. The imidazoline I₂ receptor is an emerging drug target for analgesics. However, few studies have examined the effects of selective I₂ receptor ligands on the antinociceptive activity of opioids. This study examined the antinociceptive effects of the opioids morphine (0.1–10mg/kg) and tramadol (3.2–56mg/kg), the nonselective I₂ receptor ligand agmatine (10–100mg/kg), and the selective I₂ receptor ligands 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI; 1–10mg/kg) and 2-(4, 5-dihydroimidazol-2-yl) quinoline hydrochloride (BU224; 1–10mg/kg), alone and in combination, in a warm water tail withdrawal procedure in rats. Morphine and tramadol but not agmatine, 2-BFI or BU224 increased tail withdrawal latency in a dose-related manner at 48°C water. Agmatine and 2-BFI but not BU224 dose-dependently enhanced the antinociceptive effects of morphine and tramadol, shifting the dose–effect curves of morphine and tramadol leftward. The enhancement of agmatine and 2-BFI on morphine and tramadol antinociception was prevented by BU224. These results, combined with the fact that BU224 and 2-BFI share similar behavioral effects under other conditions, suggest that BU224 has lower efficacy than 2-BFI at I₂ receptors, and that the enhancement of opioid antinociception by I₂ receptor ligands depends on their efficacies.
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