Effects of adrenergic agonists and antagonists on tetrodotoxin-induced nerve block
Effects of adrenergic agonists and antagonists on tetrodotoxin-induced nerve block
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DOI：
10.1053/rapm.2001.23215
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发表时间：
2001-05-01
影响因子：
5.1
通讯作者：
Berde, CB
中科院分区：
文献类型：
--
作者：
Kohane, DS;Lu, NT;Berde, CB
背景和目的：α(1)-、α(2)-和β -肾上腺素能受体对肾上腺素能激动剂延长河豚毒素（TTX）神经阻滞的相对作用尚不清楚。我们研究了哪些受体激动剂延长TTX阻滞，以及延迟注射拮抗剂是否可以中断TTX和激动剂联合注射后延长的阻滞。方法：大鼠经皮接受120 μ mol/L TTX经皮坐骨神经阻滞治疗，联合或不联合肾上腺素能激动剂和拮抗剂。阻滞持续时间采用改良热板试验评估。使用未注射腿部的功能缺陷来评估TTX的全身分布。数据以25和75个百分位的中位数表示。结果：共注射5.5 μ mol/L苯肾上腺素（al特异性）。10 μ mol/L可乐定（α(2)特异性）和1.1 μ mol/L肾上腺素（混合α -和β -激动剂）延长TTX神经阻滞，但5.5 μ mol/L异丙肾上腺素（混合p -激动剂）没有延长TTX神经阻滞。育亨宾抑制可乐定延长TTX阻滞（中位抑制浓度，IC50 = 130 nmol/L）；酚妥拉明同样抑制肾上腺素（IC50 = 45 nmol/L）。肾上腺素能拮抗剂在初始阻滞后3或6小时注射时，不抑制激动剂延长TTX阻滞。皮下注射肾上腺素能激动剂远端部位不延长TTX阻滞，除了可乐定适度延长。结论：α(1)-和α(2)-可以延长TTX阻滞，但β -肾上腺素能激动剂不能通过相对短暂的局部介导事件延长TTX阻滞。延迟注射肾上腺素能拮抗剂不会中断TTX和肾上腺素能激动剂联合注射产生的延长阻滞，除非在阻滞建立后不久给药。
Background and Objectives: The relative contributions of alpha (1)-, alpha (2)-, and beta -adrenergic receptors to adrenergic agonists' prolongation of nerve block by tetrodotoxin (TTX) are unknown. We investigated which receptor agonists prolong TTX block, and whether delayed injection of antagonists can interrupt prolonged blocks after coinjection of TTX and agonists.Methods: Rats received percutaneous sciatic nerve block with 120 mu mol/L TTX with and without adrenergic agonists and antagonists. Block duration was assessed by a modified hot-plate test. Functional deficits in the uninjected leg were used to assess systemic distribution of TTX. Data were expressed as medians with 25th and 75th percentiles.Results: Coinjection of 5.5 mu mol/L phenylephrine (al-specific). 10 mu mol/L clonidine (alpha (2)-specific), and 1.1 mu mol/L epinephrine (mixed alpha- and beta -agonist) prolonged TTX nerve block, but 5.5 mu mol/L isoproterenol (mixed P-agonist) did not. Yohimbine inhibited TTX block prolongation by clonidine (median inhibitory concentrations, IC50 = 130 nmol/L); phentolamine similarly inhibited epinephrine (IC50 = 45 nmol/L). Adrenergic antagonists did not inhibit the prolongation of TTX block by agonists when injected 3 or 6 hours after the initial block. Subcutaneous injection of adrenergic agonists at a remote site did not prolong TTX block, except for a modest prolongation by clonidine.Conclusions: TTX block can be prolonged by alpha (1)- and alpha (2)-, but not beta -adrenergic agonists via locally mediated events of relatively brief duration. Delayed injection of adrenergic antagonists does not interrupt the prolonged blocks produced by coinjection of TTX and adrenergic agonists unless administered soon after block is established.