Yoon M H, Choi J I, Kim S J, Kim C M, Bae H B, Chung S T
Chonnam National University, Medical School, Department of Anesthesiology and Pain Medicine, Gwangju, Korea.
Eur J Anaesthesiol. 2006 Jan;23(1):65-70. doi: 10.1017/S0265021505001791.
The cyclic guanosine monophosphate level, which causes an antinociception, is increased in cells as a direct result of phosphodiesterase inhibition. This study used a nociceptive test to examine the nature of the pharmacological interaction between intrathecal zaprinast, a phosphodiesterase inhibitor, and morphine.
Catheters were inserted into the intrathecal space through an incision in the atlantooccipital membrane of male Sprague-Dawley rats. As a nociceptive model, 50 microL of a 5% formalin solution was injected into the hind paw. After observing the effect of zaprinast (37, 111, 369 nmol) and morphine (1, 4, 10, 40 nmol) alone, the interactions of their combination were examined by an isobolographic analysis.
Intrathecal zaprinast (P < 0.05) and morphine (P < 0.05) dose-dependently suppressed the flinching observed during phase 1 and phase 2 in the formalin test. The ED50 values (95% confidence intervals) of zaprinast and morphine in phase 1 were 161.9 (87.9-298.3) and 11.6 nmol (4.8-27.9 nmol), respectively. The phase 2 ED50 values (95% confidence intervals) of zaprinast and morphine were 229.9 (142.5-370.9) and 3.9 nmol (1.9-7.6 nmol), respectively. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery a zaprinast-morphine mixture in both phases. The ED50 values of (95% confidence intervals) zaprinast in the combination of zaprinast with morphine in phase 1 and phase 2 were 14.2 (4.9-40.6) and 10.4 nmol (3-35.9 nmol), respectively.
Intrathecal zaprinast and morphine are effective against acute pain and facilitated pain state. Zaprinast interacts synergistically with morphine.
磷酸二酯酶抑制可直接导致细胞内环磷酸鸟苷水平升高，进而产生抗伤害感受作用。本研究采用伤害感受测试，以探究鞘内注射扎普司特（一种磷酸二酯酶抑制剂）与吗啡之间的药理相互作用性质。
通过雄性Sprague-Dawley大鼠寰枕膜切口将导管插入鞘内空间。作为伤害感受模型，将50微升5%福尔马林溶液注射到后爪。在观察扎普司特（37、111、369纳摩尔）和吗啡（1、4、10、40纳摩尔）单独作用的效果后，通过等高线图分析检测它们联合使用时的相互作用。
鞘内注射扎普司特（P < 0.05）和吗啡（P < 0.05）剂量依赖性地抑制了福尔马林试验第1阶段和第2阶段观察到的退缩反应。扎普司特和吗啡在第1阶段的半数有效剂量（ED50）值（95%置信区间）分别为161.9（87.9 - 298.3）和11.6纳摩尔（4.8 - 27.9纳摩尔）。扎普司特和吗啡在第2阶段的ED50值（95%置信区间）分别为229.9（142.5 - 370.9）和3.9纳摩尔（1.9 - 7.6纳摩尔）。等高线图分析显示，鞘内注射扎普司特 - 吗啡混合物后在两个阶段均存在协同相互作用。扎普司特与吗啡联合使用时在第1阶段和第2阶段的ED50值（95%置信区间）分别为14.2（4.9 - 40.6）和10.4纳摩尔（3 - 35.9纳摩尔）。
鞘内注射扎普司特和吗啡对急性疼痛和易化疼痛状态有效。扎普司特与吗啡存在协同相互作用。
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