title: Effect of BU98008, an imidazoline1-binding site ligand, on body temperature in mice.
abstract: Previous studies using the novel imidazoline1-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 imidazoline1-binding site ligand with 300 fold selectively for the imidazoline1-binding site relative to alpha2-adrenoceptors. However, alpha2-adrenoceptor agonists are known to induce hypothermia, therefore, the present study has investigated the ability of the selective alpha2-adrenoceptor antagonist, RX811059 (2-ethoxy idazoxan) and the mixed imidazoline1-binding site/alpha2-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 imidazoline1-binding site. Body temperature may therefore provide a novel assay for investigating agonist and antagonist action at the imidazoline1-binding site.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University Walk, Clifton, Bristol BS8 1TD, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: Cambridge
authors.forename: Emma S J
authors.initials: ES
authors.lastname: Robinson
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001665:Binding Sites; D001831:Body Temperature / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology*; D054755:Imidazoline Receptors; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D051379:Mice; D011955:Receptors, Drug / Q000378:metabolism
chemical_list: C483907:1-(4,5-dihydro-1H-imidazol-2-yl)isoquinoline; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D007546:Isoquinolines; D008024:Ligands; D011955:Receptors, Drug; C410887:imidazoline I1 receptors; C065483:ethoxyidazoxan; C062597:efaroxan; D019329:Idazoxan