Kissin I, Brown P T, Robinson C A, Bradley E L
Department of Anesthesiology, University of Alabama School of Medicine, Birmingham 35294.
Anesth Analg. 1991 Nov;73(5):619-21. doi: 10.1213/00000539-199111000-00018.
To demonstrate the development of acute tolerance to the hypnotic effects of morphine, loss and recovery of the righting reflex with a constant-rate morphine infusion was studied in rats. In one group of animals, brain and serum concentrations of morphine were detected (radioimmunoassay) at the time of loss of the righting reflex, and in another group, at the time of the reflex recovery. The morphine infusion at a constant rate of 14 mg.kg-1.h-1 caused a loss of the righting reflex in all animals that was achieved by 2.5 h. However, this level of response could not be maintained, and at 5 h it began to decline. All animals recovered the righting reflex by the ninth hour, despite the continuing morphine infusion. The morphine brain and serum levels at the times of loss and recovery of the righting reflex were not different. The results suggest a development of acute tolerance to the hypnotic effect of morphine, which is determined primarily by pharmacodynamic mechanisms.
为了证明对吗啡催眠作用急性耐受性的发展，我们在大鼠中研究了以恒定速率输注吗啡时翻正反射的丧失和恢复情况。在一组动物中，在翻正反射丧失时检测脑和血清中的吗啡浓度（放射免疫测定），在另一组动物中，在反射恢复时进行检测。以14mg·kg-1·h-1的恒定速率输注吗啡会导致所有动物在2.5小时时出现翻正反射丧失。然而，这种反应水平无法维持，在5小时时开始下降。尽管吗啡持续输注，但所有动物在第九小时时恢复了翻正反射。翻正反射丧失和恢复时的吗啡脑浓度和血清浓度并无差异。结果表明对吗啡催眠作用产生了急性耐受性，这主要由药效学机制决定。
