Rundlett Beyer J, Elliott H W
J Pharmacol Exp Ther. 1976 Aug;198(2):330-9.
In this comparative study, the abdominal constriction test was used to determine analgesia in mice, and the body plethysmograph was used to study respiratory effects of nalodeine, nalorphine, naloxone, codeine, morphine and various agonist-antagonist combinations in rats. The analgesia dose-response curves for the surrogate pairs, nalodeine-nalorphine and codeine-morphine, were parallel but had significantly different slopes. Naloxone was a more potent antagonist of morphine and codeine than of nalorphine and nalodeine. In antagonizing morphine and codeine analgesia, naloxone was the most potent antagonist, nalorphine had a biphasic effect with decreasing activity at higher doses and nalodeine was not an antagonist. Moderate doses of nalorphrine depressed minute volume largely by their effect on tidal volume, but high doses stimulated respiratory rate and therefore had less effect on minute volume. Nalodeine depressed minute volume by depressing tidal volume, since all doses initially stimulated and then variably affected respiratory rate. Metabolic rate was not increased by either drug short of convulsant doses. Nalodeine depresses the ventilatory response to CO2 and weakly antagonizes the respiratory depressant actions of morphine.
在这项比较研究中,采用腹部收缩试验来测定小鼠的镇痛效果,并使用体容积描记仪研究纳洛地因、纳洛芬、纳洛酮、可待因、吗啡以及各种激动剂 - 拮抗剂组合对大鼠呼吸的影响。替代对纳洛地因 - 纳洛芬和可待因 - 吗啡的镇痛剂量 - 反应曲线是平行的,但斜率有显著差异。纳洛酮对吗啡和可待因的拮抗作用比对纳洛芬和纳洛地因更强。在拮抗吗啡和可待因的镇痛作用方面,纳洛酮是最有效的拮抗剂,纳洛芬具有双相作用,在较高剂量时活性降低,而纳洛地因不是拮抗剂。中等剂量的纳洛芬主要通过对潮气量的影响来降低分钟通气量,但高剂量会刺激呼吸频率,因此对分钟通气量的影响较小。纳洛地因通过降低潮气量来降低分钟通气量,因为所有剂量最初都会刺激呼吸频率,随后对其产生不同程度的影响。在未达到惊厥剂量时,两种药物均未增加代谢率。纳洛地因会抑制对二氧化碳的通气反应,并微弱地拮抗吗啡的呼吸抑制作用。