Kovács G L, Szontágh L, Baláspiri L, Telegdy G
Peptides. 1983 Jul-Aug;4(4):417-9. doi: 10.1016/0196-9781(83)90042-6.
Effects of various dipeptides on naloxone-precipitated morphine withdrawal were studied in the mouse. Mice were rendered dependent on morphine by implantation of morphine pellets and the withdrawal syndrome was measured by the latency of the onset of stereotyped jumpings. In accordance with previous data, subcutaneous injection of Z-prolyl-D-leucine significantly delayed the onset of morphine withdrawal. The all-L enantiomer of the dipeptide (Z-L-prolyl-L-leucine) did not affect morphine withdrawal in the dose studied. Replacement of L-proline by L-glutamate or L-pyroglutamate (Z-L-glutamyl-L-leucine and L-pyroglutamyl-L-leucine) resulted in dipeptides which were more potent towards morphine withdrawal than Z-prolyl-D-leucine. Z-L-glycyl-L-proline attenuated the morphine withdrawal syndrome more effectively than Z-L-prolyl-D-leucine, but Z-L-leucyl-L-glycine was ineffective in this respect. The data reveal that certain dipeptides--which in their nonprotected forms are normal sequences of endogenous peptides--affect morphine withdrawal more potently than Z-prolyl-D-leucine, a synthetic dipeptide known to attenuate morphine dependence.
在小鼠中研究了各种二肽对纳洛酮诱发的吗啡戒断反应的影响。通过植入吗啡丸使小鼠对吗啡产生依赖性，并通过刻板跳跃发作的潜伏期来测量戒断综合征。与先前的数据一致，皮下注射Z-脯氨酰-D-亮氨酸可显著延迟吗啡戒断的发作。该二肽的全L对映体（Z-L-脯氨酰-L-亮氨酸）在所研究的剂量下不影响吗啡戒断反应。用L-谷氨酸或L-焦谷氨酸取代L-脯氨酸（Z-L-谷氨酰-L-亮氨酸和L-焦谷氨酰-L-亮氨酸）得到的二肽对吗啡戒断反应的作用比Z-脯氨酰-D-亮氨酸更强。Z-L-甘氨酰-L-脯氨酸比Z-脯氨酰-D-亮氨酸更有效地减轻吗啡戒断综合征，但Z-L-亮氨酰-L-甘氨酸在这方面无效。数据表明，某些二肽——其未保护形式是内源性肽的正常序列——比Z-脯氨酰-D-亮氨酸更有效地影响吗啡戒断反应，Z-脯氨酰-D-亮氨酸是一种已知可减轻吗啡依赖性的合成二肽。
