Porreca F, Cowan A, Tallarida R J
Eur J Pharmacol. 1981 Nov 19;76(1):55-9. doi: 10.1016/0014-2999(81)90008-x.
The kinetic profile and half-life of naloxone were studied for possible use in determination of pA2 and KB in vivo. Rats were given morphine subcutaneously and after 15 min naloxone or saline, intracerebroventricularly. A further 15 min later, and at 15 min intervals up to 135 min after morphine, the animals were tested for analgesia in the tail flick test. The dose-response curves of the naloxone group were shifted to the right of those for the saline group. The amount of displacement decreased with time, indicative of the disappearance of naloxone. The graph of log (dose ratio-1) vs. time was linear with negative slope, in agreement with the time-dependent form of the equation for competitive antagonism. From this slope, the half-life of naloxone was calculated to be 13.3 min. These results demonstrate that the time-dependent method is useful in obtaining the kinetics of centrally acting opiate antagonists.
研究了纳洛酮的动力学特征和半衰期，以探讨其在体内测定pA2和KB的可能性。给大鼠皮下注射吗啡，15分钟后经脑室注射纳洛酮或生理盐水。再过15分钟后，在注射吗啡后每隔15分钟直至135分钟，通过甩尾试验检测动物的镇痛情况。纳洛酮组的剂量反应曲线相对于生理盐水组向右移动。位移量随时间减少，表明纳洛酮消失。log（剂量比 - 1）对时间的曲线呈负斜率线性关系，符合竞争性拮抗作用方程的时间依赖性形式。根据该斜率计算出纳洛酮的半衰期为13.3分钟。这些结果表明，时间依赖性方法有助于获取中枢作用阿片类拮抗剂的动力学信息。
