ENHANCEMENT OF MORPHINE ANALGESIA BY FENFLURAMINE IN SUBJECTS RECEIVING TAILORED OPIOID INFUSIONS
ENHANCEMENT OF MORPHINE ANALGESIA BY FENFLURAMINE IN SUBJECTS RECEIVING TAILORED OPIOID INFUSIONS
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DOI：
10.1016/0304-3959(93)90118-9
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发表时间：
1993-01-01
期刊：
影响因子：
7.4
通讯作者：
CHAPMAN, CR
中科院分区：
文献类型：
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作者：
CODA, BA;HILL, HF;CHAPMAN, CR
我们评估了芬氟拉明（一种5 -羟色胺释放剂）通过静脉注射增加吗啡镇痛效力的能力。10名正常志愿者参加了4次试验，在不同的日期进行不同的治疗：(1)口服安慰剂/生理盐水输注，(2)口服安慰剂/吗啡输注，(3)口服芬氟拉明(60 mg)/生理盐水输注，(4)口服芬氟拉明/吗啡输注。在测试期间，受试者经历了反复的牙齿电刺激，强度强但可以忍受。在涉及吗啡的2天试验中，阿片类药物通过计算机泵系统给药，该系统利用个体药代动力学参数实现连续、稳定的血浆浓度接近目标值16、32和64 ng吗啡/ml；每次吗啡浓度平台维持45 min。在生理盐水输注日，我们的程序与吗啡试验日相同，只是输注的液体不含药物。所有疗程的结果测量包括受试者疼痛强度评分、牙齿诱发电位（EP）振幅和主观副作用强度（恶心、警觉性、头晕、瘙痒、情绪）的视觉模拟量表（VAS）评分。我们在基线和每个吗啡浓度平台或生理盐水输注的相应时间获得这些指标。在阿片类药物输注过程中，芬氟拉明明显增加吗啡的镇痛效力，而单独使用芬氟拉明产生的镇痛作用为临界。单独使用芬氟拉明会轻微降低警觉性，但不会显著增加吗啡的副作用。因此，我们得出结论，芬氟拉明增强了吗啡的镇痛效力，而没有平行增加阿片类药物的副作用效力。
We evaluated the ability of fenfluramine, a serotonin releaser, to increase the analgesic potency of morphine administered by tailored i.v. infusion. Ten normal volunteers participated in 4 test sessions, involving different treatments on different days: (1) oral placebo/saline infusion, (2) oral placebo/morphine infusion, (3) oral fenfluramine (60 mg)/saline infusion, and (4) oral fenfluramine/morphine infusion. Subjects experienced repetitive painful dental electrical stimuli at strong but tolerable intensities during testing. On the 2 test days involving morphine, the opioid was administered by a computer-pump system that used individual pharmacokinetic parameters to achieve consecutive, steady plasma concentrations near target values of 16, 32 and 64 ng morphine/ml; each morphine concentration plateau was maintained for 45 min. On the saline infusion days, our procedures were identical to morphine test days except that the infused fluid contained no drug. For all sessions outcome measures included subject ratings of pain intensity, dental evoked potential (EP) amplitude, and visual analog scale (VAS) ratings of subjective side-effect intensities (nausea, alertness, dizziness, itching, mood). We obtained these measures during baseline and at each morphine concentration plateau or at corresponding times during saline infusions. Fenfluramine significantly increased the analgesic potency of morphine during the opioid infusion, while fenfluramine alone produced borderline analgesic effects. Fenfluramine alone decreased alertness slightly, but did not significantly increase morphine side effects. Thus, we conclude that fenfluramine enhances the analgesic potency of morphine without a parallel increase in opioid side-effect potency.