Characterization of the hypothermic effects of imidazoline I2 receptor agonists in rats
Article first published online: 27 JUN 2012
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society
British Journal of Pharmacology
Volume 166, Issue 6, pages 1936–1945, July 2012
How to Cite
Thorn, D. A., An, X.-F., Zhang, Y., Pigini, M. and Li, J.-X. (2012), Characterization of the hypothermic effects of imidazoline I2 receptor agonists in rats. British Journal of Pharmacology, 166: 1936–1945. doi: 10.1111/j.1476-5381.2012.01894.x
- Issue published online: 27 JUN 2012
- Article first published online: 27 JUN 2012
- Accepted manuscript online: 10 FEB 2012 04:28PM EST
- Received; 7 October 2011; Revised; 24 January 2012; Accepted; 3 February 2012
- imidazoline I2 receptor;
- drug combination;
BACKGROUND AND PURPOSE Imidazoline I2 receptors have been implicated in several CNS 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.
EXPERIMENTAL APPROACH Different groups of rats were used to examine the effects of I2 receptor agonists on the rectal temperature and locomotion. The pharmacological mechanisms were investigated by combining I2 receptor ligands and different antagonists.
KEY RESULTS All the selective I2 receptor agonists examined (2-BFI, diphenyzoline, phenyzoline, CR4056, tracizoline, BU224 and S22687, 3.2–56 mg·kg–1, i.p.) dose-dependently and markedly decreased the rectal temperature (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, selective I1 receptor antagonist efaroxan, α2 adrenoceptor antagonist/5-HT1A receptor agonist yohimbine. Idazoxan but not yohimbine or efaroxan attenuated the hypothermic effects of 2-BFI, BU224, tracizoline and diphenyzoline, supporting the I2 receptor mechanism. In contrast, both idazoxan and yohimbine attenuated hypothermia induced by the α2 adrenoceptor agonist clonidine. Among all the I2 receptor agonists studied, only S22687 markedly increased the locomotor activity in rats.
CONCLUSIONS AND IMPLICATIONS Imidazoline I2 receptor agonists can produce hypothermic effects, which are primarily mediated by I2 receptors. These data suggest that I2 receptor agonist-induced hypothermia is a simple and sensitive in vivo assay for studying I2 receptor ligands.