BU-224 produces spinal antinociception as an agonist at imidazoline I-2 receptors

被引:44
作者
Diaz, A [1 ]
Mayet, S [1 ]
Dickenson, AH [1 ]
机构
[1] UCL, DEPT PHARMACOL, LONDON WC1E 6BT, ENGLAND
基金
英国惠康基金;
关键词
imidazoline receptor; BU-224 (2-(4,5-dihydroimidazol-2yl)-quinoline hydrochloride)); nociception; spinal cord; (rat);
D O I
10.1016/S0014-2999(97)01118-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In this electrophysiological study, the effect of BU-224 (2-(4,5-dihydroimidazol-2yl)-quinoline hydrochloride)), a novel high affinity imidazoline 1(2) receptor ligand, was tested on the responses of nociceptive neurones in the spinal dorsal horn. When applied spinally, akin to an intrathecal application (i.t.), BU-224 (5-250 mu g) reduced the nociceptive responses of dorsal horn neurones, producing a dose-dependent inhibition of C-fibre evoked responses, postdischarge and wind-up of the cells. A complete block of the antinociceptive effects was produced when idazoxan (100 mu g), with both alpha(2)-adrenoceptor and imidazoline I-2 receptor antagonist actions, was administered i.t. 10 min prior to the maximal dose of BU-224 tested. The nonselective alpha(2)-adrenoceptor antagonist, yohimbine (150 mu g) only partially attenuated the inhibitory effects of BU-224 when administered i.t. 10 min prior. The highly selective alpha(2)-adrenoceptor antagonist, atipamezole (100 mu g) produced no greater reversal than yohimbine under the same conditions. Although BU-224 has been reported to possess high affinity for imidazoline I-2 receptors, a minor action at spinal alpha(2)-adrenoceptor receptors cannot be discounted. These results demonstrate that BU-224 is an agonist and that imidazoline I-2 receptors, present in the dorsal horn, might play a role in spinal nociception, although further studies are needed to fully elucidate their functional roles. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:9 / 15
页数:7
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