Leedham J A, Doak N, Taylor D A, Fleming W W
Department of Pharmacology and Toxicology, West Virginia University, Morgantown 26506.
Life Sci. 1989;45(16):1483-9. doi: 10.1016/0024-3205(89)90039-8.
Chronic treatment with morphine results in a reduction in the potency of morphine in the longitudinal smooth muscle-myenteric plexus of the guinea-pig ileum. Implantation of morphine pellets leads to the development of tolerance to the inhibitory effects of morphine upon neurogenic contractions of this preparation. Tolerance develops within 24 hours, peaks between days 4 and 7 and disappears by day 14. A similar time course for the development of tolerance to the inhibitory effects of 2-chloroadenosine is also seen in these same morphine-tolerant preparations. The rate of reversal of morphine tolerance was assessed after the removal of the morphine pellets four days after implantation. In this situation, tolerance to the effects of morphine were maintained for at least 24 hours, were partially reversed at day 2 and were totally reversed by day 4. The delay in the development and reversal of the effect are consistent with the fact that chronic treatment with morphine evokes an adaptive sensitivity change.
长期用吗啡治疗会导致吗啡对豚鼠回肠纵行平滑肌-肠肌丛的效力降低。植入吗啡丸会导致对吗啡对该制剂神经源性收缩的抑制作用产生耐受性。耐受性在24小时内形成，在第4至7天达到峰值，并在第14天消失。在这些相同的吗啡耐受制剂中，对2-氯腺苷抑制作用的耐受性发展也有类似的时间进程。在植入吗啡丸4天后取出吗啡丸后，评估吗啡耐受性的逆转速率。在这种情况下，对吗啡作用的耐受性至少维持24小时，在第2天部分逆转，在第4天完全逆转。作用发展和逆转的延迟与长期用吗啡治疗引起适应性敏感性变化这一事实一致。
