脊髓以上多巴胺D_2受体介导左旋四氢巴马汀的镇痛作用<英文>  

Supraspinal D_2 receptor involved in antinociception induced by Z-tetrahydropalmatine

作　　者：胡江元[1] 金国章[1] 

机构地区：[1]中国科学院上海药物研究所,上海中国200031

出　　处：《中国药理学报》1999年第8期715-719,共5页Acta Pharmacologica Sinica

基　　金：Project supported by the National Natural Science Foundation of China, № 39670829 and № 39600179,;State Key Laboratory of Drug Research, K 016.

摘　　要：目的:研究DA受体与左旋四氢巴马汀(l-THP)镇痛作用的关系,以阐明l-THP的镇痛机制。方法:腹腔(ip)与鞘内(ith)给药,以大鼠甩尾反应观测热伤害性致痛阈。结果:ip l-THP或D_2受体拮抗剂螺哌隆产生剂量依赖性镇痛效应,并能被D_2受体激动剂喹吡罗翻转,但不被纳洛酮翻转。而ithl-THP或螺哌隆无镇痛效应,但它们能拮抗ith喹吡罗引起的镇痛效应。结论:激动脊髓D_2受体或阻滞脊髓以上水平D_2受体均产生镇痛效应;l-THP镇痛作用通过阻滞脊髓以上D_2受体实现。AIM: To study the role of dopamine (DA) receptors in l-tetrahydropalmatine (l-THP)-induced antinociception. METHODS: The intraperitoneal ( ip) and intrathecal (ith) injections were used to give the drugs. The tail-flick test was used to assess the nociceptive threshold of rats. RESULTS: By ip injection, l-THP (10, 20, 40 mg·kg-1) as well as D2 receptor antagonist spiperone (1, 2, 3 mg·kg-1) produced dose-dependent antinociceptive effects on the nocicep-tion of rats, while D2 receptor agonist quinpirole, D1 receptor agonist SKF38393, and D1 receptor antagonist Sch-23390 showed no antinociception. Moreover, l-THP- or spiperone-induced antinociception was markedly attenuated by quinpirole (2, 3 mg·kg-1) but not SKF38393 or naloxone. On the other hand, ith quinpirole (20, 30, 40 μg·kg-1) also induced a dose-dependent antinociception, while ith l-THP, spiperone, SKF38393, and Sch-23390 did not exhibit any antinociception. Furthermore, ith spiperone (20, 30, 40 μg·kg-1) but not Sch-23390 dose-dependently antagonised the antinociception induced by quinpirole. l-THP (ith, 100, 200, 300 μg·kg-1) also dramatically attenuated the quinpirole-induced antinociception with a dose-dependent relationship. CONCLUSION:Activating the spinal D2 receptor or blocking the supraspinal D2 receptor produces antinociception. D1 receptor might be not directly involved in the antinociception. l-THP (as a D2 antagonist) as well as spiperone produces antinociception via blocking the supraspinal D_2 receptor.

关 键 词：四氢巴马汀 多巴胺受体 非麻醉性镇痛药 药理 

分 类 号：R971.1[医药卫生—药品]