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Characterization of imidazoline I2 receptor agonists‐induced hypothermia in rats
Author(s) -
Thorn David A.,
An Xiao-Fei,
Zhang Yanan,
Pigini Maria,
Li Jun-Xu
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1043.5
Subject(s) - idazoxan , imidazoline receptor , yohimbine , agonist , pharmacology , hypothermia , chemistry , endocrinology , receptor , receptor antagonist , medicine , clonidine , antagonist , biology , prazosin , biochemistry
Imidazoline I2 receptors have been implicated in several central nervous system disorders. Although several I2 receptor agonists have been described, no simple and sensitive in vivo bioassay is available for studying I2 receptor ligands. This study examined I2 receptor agonist‐induced hypothermia as a functional in vivo assay of I2 receptor agonism in rats. All the selective I2 receptor agonists examined (2‐BFI, diphenyzoline, phenyzoline, CR4056, tracizoline, BU224 and S22687 , 3.2–56 mg/kg, i.p) dose‐dependently produced hypothermia in rats, with varied duration of action. Pharmacological mechanism of the observed hypothermia was studied by combining the I2 receptor agonists (2‐BFI, BU224, tracizoline and diphenyzoline) with imidazoline I2 receptor/α2 adrenoceptor antagonist idazoxan or α2 adrenoceptor antagonist/serotonergic 5‐HT1A receptor agonist yohimbine. Idazoxan but not yohimbine attenuated the hypothermic effects of 2‐BFI, BU224, tracizoline and diphenyzoline, supporting the I2 receptor mechanism. In contrast, both idazoxan and yohimbine attenuated the α2 adrenoceptor agonist clonidine induced hypothermia. Together, these data suggest that imidazoline I2 receptor agonists can produce hypothermic effects, which may be useful as a simple and sensitive in vivo assay for studying I2 receptor ligands.