塞来昔布对脑啡肽降解酶的抑制作用可能是其抗焦虑活性的一种机制。

The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity.

作者信息

Zozulya A A, Kost N V, Yu Sokolov O, Gabaeva M V, Grivennikov I A, Andreeva L N, Zolotarev Y A, Ivanov S V, Andryushchenko A V, Myasoedov N F, Smulevich A B

机构信息

Center of Mental Health, Russian Academy of Medical Sciences, Moscow.

出版信息

Bull Exp Biol Med. 2001 Apr;131(4):315-7. doi: 10.1023/a:1017979514274.

DOI:10.1023/a:1017979514274

PMID:11550013

Abstract

Examination of patients with various forms of anxiety and phobic disorders (according to DSM-4 criteria) demonstrated a considerable shortening of enkephalin half-life and reduced total enkephalinase activity in the blood during generalized anxiety, but not during panic disorders and agoraphobia. This was probably related to low blood concentration of endogenous inhibitors of enkephalin-degrading enzymes in patients with generalized anxiety disorders. Heptapeptide Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), which attenuates behavioral anxiety reactions and does not cause side effects typical of most anxiolytics, dose-dependently inhibited enzymatic hydrolysis of plasma enkephalin (IC50 15 microM). Selank was more potent than peptidase inhibitors bacitracin and puromycin in inhibiting enkephalinases. These results suggest that high efficiency of Selank in the therapy of anxiety and phobic disorders, including generalized anxiety, is due to its ability to inhibit enkephalin hydrolysis.

摘要

对患有各种形式焦虑症和恐惧症（根据DSM-4标准）的患者进行检查发现，在广泛性焦虑期间，脑啡肽半衰期显著缩短，血液中脑啡肽酶总活性降低，但在惊恐障碍和广场恐惧症期间未出现这种情况。这可能与广泛性焦虑症患者血液中脑啡肽降解酶内源性抑制剂的低浓度有关。七肽塞兰克（苏氨酸-赖氨酸-脯氨酸-精氨酸-脯氨酸-甘氨酸-脯氨酸）可减轻行为焦虑反应，且不会引起大多数抗焦虑药典型的副作用，它能剂量依赖性地抑制血浆脑啡肽的酶促水解（IC50为15微摩尔）。在抑制脑啡肽酶方面，塞兰克比肽酶抑制剂杆菌肽和嘌呤霉素更有效。这些结果表明，塞兰克在治疗焦虑症和恐惧症（包括广泛性焦虑症）方面的高效性归因于其抑制脑啡肽水解的能力。