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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >The effect of cumulative dosing on the analgesic potency of morphine in mice.
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The effect of cumulative dosing on the analgesic potency of morphine in mice.

机译：累积剂量对吗啡镇痛作用的影响。

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Opioid analgesic potency can be evaluated using cumulative dosing, in which subjects are repeatedly administered a drug and tested after each dose until a criterion effect is reached. Although many laboratories use cumulative dosing, the effects of varying the starting dose and the magnitude of the increment dose on morphine analgesia (tail flick) in mice have not been evaluated. In experiment 1. mice were injected with the same starting dose [0.5 mg/kg subcutaneously (SC)] and 30 min later were tested for analgesia. Mice that were not analgesic were administered an increment dose (0.5, 1.0, 2.0, 2.5, or 3.0 mg/kg) and retested. The process was continued until all mice were analgesic. There was a significant effect of increment dose on morphine potency, with the relative potency increasing as the increment dose was increased. In experiment 2, different starting doses (0.5, 1.0, 2.0, or 3.0 mg/kg) were used with a constant increment dose of 1.0 mg/kg. There was a significant effect of starting dose on the potency of morphine, with the relative potency increasing as the starting dose increased. To determine if increment and starting dose affect tolerance estimates, mice were implanted SC with a 25- or 75-mg morphine or placebo pellet for 7 days and then tested using cumulative dose-response. Changes in the increment dose significantly affected the degree of tolerance for mice implanted with a 25-mg morphine pellet but not for mice implanted with a 75-mg morphine pellet. Changes in the starting dose did not significantly alter estimates of tolerance. Overall, these data indicate that the starting dose and increment dose can impact on morphine's potency determined by cumulative dosing protocols. Furthermore, estimates of tolerance can be affected by dosing parameters in the cumulative dosing protocol. These results suggest that cumulative dosing procedures should be standardized across experiments.
机译：可以使用累积剂量来评估阿片类药物的镇痛效果，在这种方式中，反复给对象施用药物并在每次给药后进行测试，直到达到标准效果为止。尽管许多实验室使用累积剂量，但尚未评估改变起始剂量和增量剂量的幅度对小鼠吗啡镇痛（甩尾）的影响。在实验1.中，给小鼠注射相同的起始剂量[0.5 mg / kg皮下注射（SC）]，然后在30分钟后测试镇痛效果。对非镇痛小鼠给予增量剂量（0.5、1.0、2.0、2.5或3.0 mg / kg）并重新测试。该过程一直持续到所有小鼠都止痛为止。增量剂量对吗啡效价有显着影响，相对效能随增量剂量的增加而增加。在实验2中，以1.0 mg / kg的恒定增量剂量使用了不同的起始剂量（0.5、1.0、2.0或3.0 mg / kg）。起始剂量对吗啡的效力有显着影响，相对效力随起始剂量的增加而增加。为了确定增量和起始剂量是否会影响耐受性估计，将25毫克或75毫克吗啡或安慰剂小球植入SC小鼠7天，然后使用累积剂量反应进行测试。增量剂量的变化会显着影响植入25 mg吗啡药丸的小鼠的耐受程度，但不会影响植入75 mg吗啡药丸的小鼠的耐受程度。起始剂量的变化并没有明显改变耐受性的估计。总体而言，这些数据表明起始剂量和增量剂量会影响由累积给药方案确定的吗啡效价。此外，累积剂量方案中的剂量参数可能会影响公差估计。这些结果表明，累积剂量程序应在整个实验中标准化。

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