Pharmacological profiles of alpha 2 adrenergic receptor agonists identified using genetically altered mice and isobolographic analysis.
Pharmacological profiles of alpha 2 adrenergic receptor agonists identified using genetically altered mice and isobolographic analysis.
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DOI：
10.1016/j.pharmthera.2009.04.001
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发表时间：
2009-08
影响因子：
13.5
通讯作者：
Wilcox, George L.
中科院分区：
文献类型：
--
作者：
Fairbanks, Carolyn A.;Stone, Laura S.;Wilcox, George L.
内源性，下行去甲肾上腺素能纤维传递强大的镇痛控制脊髓传入回路介导疼痛信号的横向传递。这些纤维针对初级传入终端和次级神经元上的α2肾上腺素能受体（α2ARs），它们的激活介导了对这种传递的实质性抑制控制，与具有相似分布模式的阿片受体相媲美。初级传入伤害感觉神经元和次级脊髓背角神经元末梢分别表达α2AAR和α2CAR亚型。通过将药物集中在脊柱水平，这些药物的脊髓输送有助于减少其副作用，这些副作用主要是在脊柱上部位介导的。用五种选择性治疗激动剂（可口定、右美托咪定、溴莫那定、ST91和莫替定）中的一种靶向这些脊柱α 2ar，可产生显著的抗痛觉作用，并可与阿片类激动剂协同产生协同的抗痛觉作用。几种转基因小鼠系的应用有助于鉴定可能介导这些药物的抗伤害感受作用的主要受体亚型。这篇综述首先提供了三种亚型在中枢神经系统中定位的解剖学描述，其次详细介绍了这六种主要激动剂的药理学历史，最后全面报道了其他GPCR激动剂与六种主要α2AR激动剂的具体相互作用。
Endogenous, descending noradrenergic fibers convey powerful analgesic control over spinal afferent circuitry mediating the rostrad transmission of pain signals. These fibers target alpha 2 adrenergic receptors (α2ARs) on both primary afferent terminals and secondary neurons, and their activation mediates substantial inhibitory control over this transmission, rivaling that of opioid receptors which share similar a similar pattern of distribution. The terminals of primary afferent nociceptive neurons and secondary spinal dorsal horn neurons express α2AAR and α2CAR subtypes, respectively. Spinal delivery of these agents serves to reduce their side effects, which are mediated largely at supraspinal sites, by concentrating the drugs at the spinal level. Targeting these spinal α2ARs with one of five selective therapeutic agonists, clonidine, dexmedetomidine, brimonidine, ST91 and moxonidine, produces significant antinociception that can work in concert with opioid agonists to yield synergistic antinociception. Application of several genetically altered mouse lines had facilitated identification of the primary receptor subtypes that likely mediate the antinociceptive effects of these agents. This review provides first an anatomical description of the localization of the three subtypes in the central nervous system, second a detailed account of the pharmacological history of each of these six primary agonists, and finally a comprehensive report of the specific interactions of other GPCR agonists with each of the six principal α2AR agonists featured.
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影响因子：
4.7
作者：
BOURGOIN, S;POHL, M;CESSELIN, F
通讯作者：
CESSELIN, F
DOI：
10.1111/j.1365-2125.1978.tb01614.x
发表时间：
1978-01-01
影响因子：
3.4
作者：
ASHTON, H;RAWLINS, MD
通讯作者：
RAWLINS, MD
影响因子：
5.1
作者：
Chiari, A;Eisenach, JC
通讯作者：
Eisenach, JC
影响因子：
1.7
作者：
Cho, HJ;Kim, DS;Kim, KJ
通讯作者：
Kim, KJ
影响因子：
8.8
作者：
Bouaziz, H;Tong, CY;Eisenach, JC
通讯作者：
Eisenach, JC