Pharmacological evidence for different alpha2-adrenergic receptor sites mediating analgesia and sedation in the rat
Pharmacological evidence for different alpha2-adrenergic receptor sites mediating analgesia and sedation in the rat
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DOI：
10.1093/bja/81.2.208
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发表时间：
1998-08-01
影响因子：
9.8
通讯作者：
Yaksh, TL
中科院分区：
文献类型：
--
作者：
Buerkle, H;Yaksh, TL
细胞内给予α(2)-肾上腺素能激动剂可产生抗痛觉作用和脑室内镇静作用。为了研究不同α(2)-肾上腺素能受体亚型是否介导抗痛觉和镇静作用的差异，我们测量了三种α(2)-肾上腺素能激动剂右美托咪定（DMET）、可口定（CLON）和UK-14.304 （UK）在脊髓和颅腔注射后的相对效力。每种激动剂分别单独或与育亨宾一起给予，育亨宾在未麻醉的大鼠中作为竞争性α(2)拮抗剂。单用激动剂鞘内给药具有剂量依赖性的抗感觉性作用（ED50 (nmol): DMET=1.2， UK=1.7， CLON=5.6），低剂量时镇静作用很小。育亨宾预处理导致剂量-反应曲线右移（DMET>CLON>UK）。ICV α(2)-肾上腺素能激动剂产生剂量依赖性镇静作用(ED50 (nmol): DMET=10.5；英国= 28.7;CLON=126)，抗感受性作用小。育亨宾预处理再次导致ICV镇静剂量-反应曲线右移（UK>DMET>CLON）。因此，我们得出结论，DMET、CLON和UK的脊髓镇痛作用似乎是由两个部位介导的。ICV分娩后，DMET CLON和UK似乎在一个共同的脊髓上部位产生镇静作用，这个部位类似于UK在脊髓中的作用。
Alpha(2)-adrenergic agonists given intrathecally result in antinociception and intracerebroventricularly (ICV) in sedation. To examine whether different alpha(2)-adrenergic receptor subtypes differentially mediate antinociception and sedation, we measured the relative potency of three alpha(2)-adrenergic agonists, dexmedetomidine (DMET), clonidine (CLON) and UK-14.304 (UK), after spinal and ICV administration. Each agonist was given either alone or in the presence of systemically administered yohimbine, which acts as a competitive alpha(2)-antagonist in unanaesthetized rats. Intrathecal delivery of the agonists alone resulted in a dose-dependent antinociceptive effect (ED50 (nmol): DMET=1.2, UK=1.7, CLON=5.6) with little sedative effect at the lower doses. Yohimbine pretreatment resulted in a rightward shift of the dose-response curves (DMET>CLON>UK). ICV alpha(2)-adrenergic agonists produced a dose-dependent sedation (ED50 (nmol): DMET=10.5; UK=28.7; CLON=126), with little antinociceptive action. Again, yohimbine pretreatment produced a right shift of the ICV sedation dose-response curves (UK>DMET>CLON). Thus, we conclude that the spinal analgesic effects of DMET, CLON and UK appear to be mediated by two sites. After ICV delivery, DMET CLON and UK appear to act at a common supra-spinal site to produce sedation and this site resembles that acted upon by UK in the spinal cord.