Behavioural effects of the novel AMPA/GluR5 selective receptor antagonist NS1209 after systemic administration in animal models of experimental pain
Behavioural effects of the novel AMPA/GluR5 selective receptor antagonist NS1209 after systemic administration in animal models of experimental pain
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DOI：
10.1016/j.neuropharm.2004.04.007
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发表时间：
2004-09-01
影响因子：
4.7
通讯作者：
Erichsen, HK
中科院分区：
文献类型：
--
作者：
Blackburn-Munro, G;Bomholt, SF;Erichsen, HK
在实验性疼痛的动物模型中测试了新型AMPA/GluR 5选择性受体拮抗剂NS 1209的全身给药效果，并与AMPA受体拮抗剂NBQX和阿片吗啡进行了比较。在小鼠热板试验中，NS 1209（3-30 mg/kg，s.c.和i. p.）和吗啡（3-30 mg/kg，s.c.）显著增加伤害性反应潜伏期，而NBQX（3-30 mg/kg，i. p.）是无效的。在大鼠福尔马林试验中，持续性疼痛模型，NS 1209（3和6 mg/kg：i. p.）和吗啡（0.5和3 mg/kg，s.c.）产生第二阶段伤害性行为的剂量依赖性减少，尽管NBQX（10和20 mg/kg，i. p.）没有效果。在神经性疼痛的慢性压迫性损伤模型中，NS 1209（3和6 mg/kg i. p.），NBQX（10和20 mg/kg，i.p.）和吗啡（3和6 mg/kg，s.c.）所有这些都降低了机械异常性疼痛和对vonFrey毛发和受伤后爪的针刺刺激的痛觉过敏反应。NS 1209和吗啡也降低了对氯乙烷刺激损伤后爪的冷过敏反应。在与抗伤害感受作用相关的剂量下，对于任何测试的药物，均未观察到对运动性能的影响，如通过旋转杆测试所确定的。因此，在一系列实验性疼痛的动物模型中，以非共济失调剂量全身施用NS 1209具有与吗啡相当的显著镇痛作用。(C)2004 Elsevier Ltd.保留所有权利。
The effects of systemic administration of the novel AMPA/GluR5 selective receptor antagonist NS1209 in animal models of experimental pain have been tested and compared with the AMPA receptor antagonist NBQX and the opiate morphine. In the mouse hot plate test, NS1209 (3-30 mg/kg, s.c. and i.p.) and morphine (3-30 mg/kg, s.c.) significantly increased the nociceptive response latency, whereas NBQX (3-30 mg/kg, i.p.) was ineffective. In the rat formalin test, a model of persistent pain, NS1209 (3 and 6 mg/kg: i.p.) and morphine (0.5 and 3 mg/kg, s.c.) produced dose-dependent reductions in second phase nociceptive behaviours, although NBQX (10 and 20 mg/kg, i.p.) was without effect. In the chronic constriction injury model of neuropathic pain, NS1209 (3 and 6 mg/kg i.p.), NBQX (10 and 20 mg/kg, i.p.) and morphine (3 and 6 mg/kg, s.c.) all reduced mechanical allodynia and hyperalgesia responses to von Frey hair and pin prick stimulation of the injured hindpaw. NS1209 and morphine also reduced cold hypersensitivity in response to ethyl chloride stimulation of the injured hindpaw. At the doses associated with anti-nociceptive actions, no effects on motor performance as determined by the rotarod test were observed for any of the drugs tested. Thus, systemic administration of NS1209 at non-ataxic doses has marked analgesic actions comparable to those of morphine in a range of animal models of experimental pain. (C) 2004 Elsevier Ltd. All rights reserved.