Ossipov M H, Harris S, Lloyd P, Messineo E, Lin B S, Bagley J
Anaquest, Division of BOC Health Care, Murray Hill, New Jersey 07974.
Anesthesiology. 1990 Dec;73(6):1227-35. doi: 10.1097/00000542-199012000-00022.
The antinociceptive interaction on the tail flick (TF) and hot plate (HP) tests between opioid analgesics and medetomidine after intravenous (iv) or intrathecal administration were examined by isobolographic analysis. Male Sprague-Dawley rats received fixed ratios of medetomidine to morphine, fentanyl, and meperidine of 1:10 and 1:30, 10:1, and 1:3, respectively, by iv administration or 10:1, 3:1 and 10:1, and 1:3 by intrathecal administration, respectively. Data were expressed as the percentage maximal possible effect (%MPE). The A50 (dose producing 50% MPE) for each drug or drug combination was determined from the dose-response curve. Isobolographic analysis revealed that the effect of medetomidine combined with fentanyl, morphine, or meperidine was additive after iv administration. The intrathecal administration of combinations of medetomidine with the opioids produced a synergistic antinociceptive effect in the TF but not HP test. These data confirmed that the interaction between medetomidine and opioids in producing antinociception may be additive or synergistic, depending on the route of administration, drug ratio administered, and level of processing of the nociceptive input (i.e., spinal vs. supraspinal). Moreover, these results were consistent with a spinal role for alpha-2 adrenoceptors in mediating antinociception. The authors suggest that the interaction between the opioid and alpha-2 adrenergic receptors occurs within the spinal cord.
通过等效应线分析，研究了静脉注射（iv）或鞘内注射后阿片类镇痛药与美托咪定在甩尾（TF）和热板（HP）试验中的抗伤害感受相互作用。雄性Sprague-Dawley大鼠分别通过静脉注射接受美托咪定与吗啡、芬太尼和哌替啶的固定比例为1:10、1:30、10:1和1:3，或分别通过鞘内注射接受10:1、3:1、10:1和1:3。数据以最大可能效应百分比（%MPE）表示。从剂量-反应曲线确定每种药物或药物组合的A50（产生50% MPE的剂量）。等效应线分析显示，静脉注射后美托咪定与芬太尼、吗啡或哌替啶联合使用的效果是相加的。鞘内注射美托咪定与阿片类药物的组合在TF试验中产生协同抗伤害感受作用，但在HP试验中未产生。这些数据证实，美托咪定与阿片类药物在产生抗伤害感受方面的相互作用可能是相加的或协同的，这取决于给药途径、给药药物比例和伤害性输入的处理水平（即脊髓与脊髓上）。此外，这些结果与α-2肾上腺素能受体在介导抗伤害感受中的脊髓作用一致。作者认为阿片类药物与α-2肾上腺素能受体之间的相互作用发生在脊髓内。
