Kovács G L, Telegdy G, Hódi K
Pharmacol Biochem Behav. 1984 Sep;21(3):345-8. doi: 10.1016/s0091-3057(84)80092-1.
The dipeptide Z-prolyl-D-leucine (Z-Pro-D-Leu) has been demonstrated to inhibit the development of tolerance to and dependence on morphine in the mouse. Since the dipeptide affects dopamine (DA) utilization in the terminal regions of the mesolimbic and nigrostriatal DA-ergic projections, the question has been studied of whether DA-ergic mechanisms are involved in the action of Z-Pro-D-Leu on morphine withdrawal. Both inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine (alpha-MPT) and inhibition of DA receptors by pimozide interfere with the effect of Z-Pro-D-Leu on naloxone-precipitated morphine withdrawal. Inhibition of serotonin (5-HT) synthesis by DL-p-chlorophenylalanine (PCPA), on the other hand, does not modify the effect of the dipeptide. The results argue for a role of DA-ergic mechanisms in the effect of Z-Pro-D-Leu on the development of morphine dependence.
二肽Z-脯氨酰-D-亮氨酸（Z-Pro-D-Leu）已被证明能抑制小鼠对吗啡耐受性和依赖性的发展。由于该二肽会影响中脑边缘和黑质纹状体多巴胺能投射终末区域的多巴胺（DA）利用，因此人们研究了多巴胺能机制是否参与Z-Pro-D-Leu对吗啡戒断的作用。α-甲基-对-酪氨酸（α-MPT）对酪氨酸羟化酶的抑制以及匹莫齐特对DA受体的抑制均会干扰Z-Pro-D-Leu对纳洛酮诱发的吗啡戒断的作用。另一方面，DL-对氯苯丙氨酸（PCPA）对血清素（5-HT）合成的抑制不会改变该二肽的作用。这些结果表明多巴胺能机制在Z-Pro-D-Leu对吗啡依赖性发展的作用中发挥了作用。
