France C P, Woods J H
J Pharmacol Exp Ther. 1985 Nov;235(2):442-7.
Pigeons trained to peck a key on a fixed-ratio 20 schedule of food presentation were used to evaluate the antagonistic and rate-suppressing effects of several opioid antagonists. Antagonism was measured as an increase in the dose of morphine necessary to suppress responding. Antagonist pretreatments increased the suppressing dose of morphine, although the magnitude of the increase varied markedly among different antagonists. Rank order of the maximum increase in the suppressing dose of morphine that each antagonist produced was: naltrexone = WIN 44,441 greater than beta-funaltrexamine greater than naloxone = buprenorphine greater than MR 2266 greater than diprenorphine. The time course of morphine antagonism also differed among antagonists. For example, buprenorphine was not an effective antagonist when administered 10 min before morphine, but was effective when administered either 2 or 12 hr before morphine. beta-Funaltrexamine and WIN 44,441 had the longest durations of antagonist action; each antagonized the rate-suppressing effects of morphine from 10 min to 24 hr. The effective antagonistic dose range (i.e., doses which blocked the rate-suppressing effects of morphine without affecting response rate when administered alone) and maximum increase in the suppressing dose of morphine were highly correlated, suggesting that the direct effects of most of these antagonists on responding may limit their effectiveness as morphine antagonists.
训练鸽子在固定比率为20的食物呈现时间表上啄击按键，以此来评估几种阿片类拮抗剂的拮抗作用和速率抑制作用。拮抗作用通过抑制反应所需吗啡剂量的增加来衡量。拮抗剂预处理增加了吗啡的抑制剂量，尽管不同拮抗剂增加的幅度差异显著。每种拮抗剂产生的吗啡抑制剂量最大增加量的排序为：纳曲酮 = WIN 44,441大于β-氟纳曲胺大于纳洛酮 = 丁丙诺啡大于MR 2266大于二丙诺啡。不同拮抗剂之间吗啡拮抗作用的时间进程也有所不同。例如，丁丙诺啡在吗啡给药前10分钟给药时不是有效的拮抗剂，但在吗啡给药前2小时或12小时给药时有效。β-氟纳曲胺和WIN 44,441具有最长的拮抗剂作用持续时间；它们在10分钟至24小时内均拮抗吗啡的速率抑制作用。有效的拮抗剂量范围（即单独给药时阻断吗啡的速率抑制作用而不影响反应速率的剂量）与吗啡抑制剂量的最大增加量高度相关，这表明这些拮抗剂中大多数对反应的直接作用可能会限制它们作为吗啡拮抗剂的有效性。
