Bentley G A, Newton S H, Starr J
Br J Pharmacol. 1981 Jun;73(2):325-32. doi: 10.1111/j.1476-5381.1981.tb10425.x.
1 A modification of the abdominal constriction test in mice has been developed, and used to study the antinociceptive effects of morphine and several related drugs. In most experiments, acetic acid (0.6% i.p.) was used as the nociceptive stimulus, and in a few cases, acetylcholine (3.2 mg/kg i.p.) was used. When the abdominal constriction response had reached a maximum, the drugs under test were given intraperitoneally, and their ability to decrease the number of abdominal constrictions was determined, beginning immediately after its administration. The aim of this study was to investigate the possibility that morphine and its congeners may produce an antinociceptive effect by an action within the peritoneum.2 It was found that morphine was an extremely potent antinociceptive agent in this modified test, with an ID(50) of 5.4 x 10(-9) mol/kg (1.54 mug/kg). Codeine and pentazocine were about 40 times less active and oxymorphine was about twice as potent as morphine. Met- and Leu-enkephalin were also potent but their action diminished very rapidly with time. Ketocyclazocine was the most potent substance tested, and had an ID(50) value of 1.26 x 10(-10) mol/kg (0.036 mug/kg). All the drugs tested produced their maximal effect within 1 or 2 min of administration.3 Pretreatment of the mice with naloxone caused a dose-dependent shift to the right of the dose-response curve to morphine. The pAx plot was linear over part of the range, with a slope of -1.02 and the ;apparent pA(2)' value was 6.14. Naloxone was much less effective in antagonizing Met-enkephalin, and caused a slight potentiation of ketocyclazocine and pentazocine and of cocaine, which was used for comparison.4 Pretreatment of mice with morphine, 3 h earlier, caused a marked tolerance to a subsequent dose of morphine, and a potentiation of the antagonist potency of naloxone. However, there was little cross-tolerance between morphine and Leu-enkephalin.5 It is concluded that morphine and its congeners can produce an antinociceptive effect by an action within the mouse peritoneum, presumably by interacting with one or more types of opioid receptors which may be situated on sensory nerve endings.
已开发出一种小鼠腹部收缩试验的改良方法，并用于研究吗啡及几种相关药物的抗伤害感受作用。在大多数实验中，使用乙酸（腹腔注射0.6%）作为伤害性刺激，在少数情况下，使用乙酰胆碱（腹腔注射3.2毫克/千克）。当腹部收缩反应达到最大值时，腹腔注射受试药物，并在给药后立即开始测定其减少腹部收缩次数的能力。本研究的目的是探讨吗啡及其同系物可能通过在腹膜内发挥作用而产生抗伤害感受作用的可能性。
发现在这种改良试验中，吗啡是一种极其有效的抗伤害感受剂，半数抑制剂量（ID50）为5.4×10⁻⁹摩尔/千克（1.54微克/千克）。可待因和喷他佐辛的活性约低40倍，羟吗啡酮的效力约为吗啡的两倍。甲硫氨酸脑啡肽和亮氨酸脑啡肽也有效，但它们的作用随时间迅速减弱。酮环唑辛是所测试的最有效的物质，ID50值为1.26×10⁻¹⁰摩尔/千克（0.036微克/千克）。所有测试药物在给药后1或2分钟内产生最大效应。
用纳洛酮预处理小鼠导致吗啡剂量-反应曲线向右剂量依赖性移动。pAx图在部分范围内呈线性，斜率为-1.02，“表观pA₂”值为6.14。纳洛酮拮抗甲硫氨酸脑啡肽的效果要差得多，并且对酮环唑辛、喷他佐辛和用于比较的可卡因有轻微的增强作用。
提前3小时用吗啡预处理小鼠，导致对随后剂量的吗啡产生明显耐受性，并增强纳洛酮的拮抗效力。然而，吗啡和亮氨酸脑啡肽之间几乎没有交叉耐受性。
得出结论，吗啡及其同系物可通过在小鼠腹膜内发挥作用产生抗伤害感受作用，大概是通过与可能位于感觉神经末梢的一种或多种阿片受体相互作用。
