Bentley G A, Newton S H, Starr J
Br J Pharmacol. 1983 May;79(1):125-34. doi: 10.1111/j.1476-5381.1983.tb10504.x.
1 A modified abdominal constriction test, whereby the drugs used are injected intraperitoneally when the writhing response is maximal, has been used to study the antinociceptive activity of various sympathomimetic drugs. Of those tested, clonidine was the most potent, with an ID(50) value in the nanomolar range. (-)-Isoprenaline, (-)-adrenaline and (-)-noradrenaline were only a little less potent. Phenylephrine, the least potent, had only about one-sixtieth of the activity of clonidine.2 The antinociceptive action appears to occur within the peritoneum, since it was apparent almost immediately after the drugs were injected and was produced by doses far smaller than were effective by the subcutaneous route.3 alpha-Adrenoceptors appear to be involved in the reaction, since noradrenaline showed stereospecificity, and the alpha-adrenoceptor antagonists phentolamine and piperoxan both shifted the dose-response curves of the alpha-adrenoceptor agonist drugs to the right, usually parallel to the control curves.4 The high antinociceptive potency of clonidine and oxymetazoline, indicate the importance of alpha(2)-adrenoceptors and this was supported by the finding that piperoxan was a more effective antagonist than phentolamine. The moderate potency of phenylephrine suggests that alpha(1)-adrenoceptors may also be involved, although the selective alpha(1)-antagonist, prazosin, did not antagonize noradrenaline and had antinociceptive activity of its own.5 beta-Adrenoceptors also appear to be involved in the antinociceptive response, since propranalol antagonized the effect of isoprenaline, but not that of clonidine.6 Piperoxan was a very effective antagonist of morphine, while phentolamine had a weaker action. Naloxone had little action against the alpha-adrenoceptor agonists.7 Mice pretreated with clonidine or oxymetazoline but not noradrenaline showed a very great cross-tolerance to morphine. Morphine pretreatment caused marked desensitization of itself, but little cross-tolerance to clonidine or oxymetazoline.8 It is suggested that sensory nerves in the mouse peritoneum have alpha(2)- and beta-adrenoceptors on their terminals, and possibly alpha(1)-receptors also. It is possible that when activated by the appropriate agonists they depress the generation of pain impulses. There is an interaction between the alpha-adrenoceptors and opioid receptors in the mouse peritoneum.
一种改良的腹部收缩试验已被用于研究各种拟交感神经药物的抗伤害感受活性。该试验是在扭体反应达到最大值时将所用药物腹腔注射。在测试的药物中，可乐定效力最强，其半数抑制剂量（ID50）值在纳摩尔范围内。（-）-异丙肾上腺素、（-）-肾上腺素和（-）-去甲肾上腺素的效力稍弱。效力最弱的去氧肾上腺素，其活性仅约为可乐定的六十分之一。
抗伤害感受作用似乎发生在腹膜内，因为在药物注射后几乎立即就很明显，而且产生这种作用所需的剂量远小于皮下给药有效的剂量。
α-肾上腺素受体似乎参与了该反应，因为去甲肾上腺素表现出立体特异性，而且α-肾上腺素受体拮抗剂酚妥拉明和哌罗克生都使α-肾上腺素受体激动剂药物的剂量-反应曲线右移，通常与对照曲线平行。
可乐定和羟甲唑啉的高抗伤害感受效力表明α₂-肾上腺素受体的重要性，哌罗克生比酚妥拉明是更有效的拮抗剂这一发现支持了这一点。去氧肾上腺素的中等效力表明α₁-肾上腺素受体可能也参与其中，尽管选择性α₁-拮抗剂哌唑嗪并不拮抗去甲肾上腺素，且自身具有抗伤害感受活性。
β-肾上腺素受体似乎也参与了抗伤害感受反应，因为普萘洛尔拮抗异丙肾上腺素的作用，但不拮抗可乐定的作用。
哌罗克生是吗啡的非常有效的拮抗剂，而酚妥拉明的作用较弱。纳洛酮对α-肾上腺素受体激动剂几乎没有作用。
用可乐定或羟甲唑啉预处理的小鼠，但不用去甲肾上腺素预处理的小鼠，对吗啡表现出非常大的交叉耐受性。吗啡预处理导致其自身明显脱敏，但对可乐定或羟甲唑啉几乎没有交叉耐受性。
有人提出，小鼠腹膜中的感觉神经末梢上有α₂-和β-肾上腺素受体，可能还有α₁-受体。当被适当的激动剂激活时，它们可能会抑制疼痛冲动的产生。小鼠腹膜中的α-肾上腺素受体和阿片受体之间存在相互作用。
