Tallarida R J, Harakal C, Maslow J, Geller E B, Adler M W
J Pharmacol Exp Ther. 1978 Jul;206(1):38-45.
When the pA2 of an antagonist is determined in vivo, administered doses are used rather than the peak or steady-state tissue concentrations. The present report examines the error which can arise in this method and also presents a method for determining the pA2 from data obtained at times after peak. We applied this time-dependent analysis to time-dose-response data obtained with morphine-naloxone in the rat, using tail compression as the nociceptive stimulus. Good agreement between pA2 values was found: 8.0 with peak effect data, and 8.1 with the time-dependent method. Further, this analysis yielded 20 minutes as the half-life of naloxone. It is concluded that the time-dependent method provides a check on the pA2 in vivo and confirms the utility of this constant in classifying receptors. The appendix contains methodology for application to other agonist-antagonist combinations classified according to their kinetics.
当在体内测定拮抗剂的pA2时，使用的是给药剂量而非峰值或稳态组织浓度。本报告研究了该方法可能出现的误差，并提出了一种根据峰值后各时间点获得的数据来确定pA2的方法。我们将这种时间依赖性分析应用于用吗啡-纳洛酮在大鼠身上获得的时间-剂量-反应数据，以尾部压迫作为伤害性刺激。发现pA2值之间有良好的一致性：与峰值效应数据相比为8.0，与时间依赖性方法相比为8.1。此外，该分析得出纳洛酮的半衰期为20分钟。结论是，时间依赖性方法可对体内的pA2进行检验，并证实了该常数在受体分类中的实用性。附录包含了应用于根据其动力学分类的其他激动剂-拮抗剂组合的方法。
