Effect of BU98008, an imidazoline1-binding site ligand, on body temperature in mice

Previous studies using the novel imidazoline(1)-binding site ligand 1-(4,5-dihydro-1H-imidazol-2-yl)isoquinoline hydrochloride, BU98008, have shown it induces a hypothermic response in rodents following intraperitoneal administration. Radioligand binding data has,shown that BU98008 is a highly selective imidazoline(1)-binding site ligand with 300 fold selectively for the imidazoline(1)-binding site relative to alpha(2)-adrenoceptors. However, alpha(2)-adrenoceptor agonists are known to induce hypothermia, therefore, the present study has investigated the ability of the selective alpha(2)-adrenoceptor antagonist, RX811059 (2-ethoxy idazoxan) and the mixed imidazoline(1)-binding site/alpha(2)-adrenoceptor antagonist, efaroxan, to attenuate the BU98008-induced hypothermia. Preliminary experiments confirmed that BU98008 induced a dose-dependent decrease in body temperature in mice at 10 and 20 mg/kg. The response was not affected by pre-treatment with RX811059 but was significantly attenuated following pre-treatment with efaroxan. These data suggest that BU98008-induced hypothermia is mediated by activation of imidazoline(1)-binding site. Body temperature may therefore provide a novel assay for investigating agonist and antagonist action at the imidazoline(1)-binding site. (c) 2005 Elsevier B.V. All rights reserved.