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神经肽:痴呆症中的促肾上腺皮质激素肽

Neuropeptides: ACTH-peptides in dementia.

作者信息

Kragh-Sørensen P, Olsen R B, Lund S, Van Riezen H, Steffensen K

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 1986;10(3-5):479-92. doi: 10.1016/0278-5846(86)90019-9.

Abstract

Studies on the treatment of demented patients with ACTH neuropeptides are reviewed. The discussion is restricted to ACTH4-10 and an orally active peptide, the modified ACTH4-9 fragment: H-Met (O2)-Glu-His-Phe-D-Lys-Phe-O (Org 2766). The first part of the review concentrates on data from animal pharmacology and basic and human studies which have relevance for the clinical effects shown in demented patients. The second part concerns clinical studies in man. Own results from a placebo-controlled dose finding study on the treatment of 156 PDSD patients with Org 2766 are presented. Org 2766 was in this study found to have a significant therapeutic effect in patients with PDSD measured mainly on the basis of SCAG total, although the effect was found to be rather small (average 4 points improvement on SCAG total). Post hoc analyses demonstrated that effects were clinically relevant for only 25 per cent of the patients. Analyses of SCAG factor scores indicated an effect on cognitive function and somatic function. The study failed to show clear dose-response relationship. However, before a final conclusion on the efficacy of Org 2766 can be reached the results must be confirmed by others.

摘要

本文综述了促肾上腺皮质激素神经肽治疗痴呆患者的研究。讨论仅限于促肾上腺皮质激素4 - 10以及一种口服活性肽,即修饰后的促肾上腺皮质激素4 - 9片段:H - 甲硫氨酸(O2)- 谷氨酸 - 组氨酸 - 苯丙氨酸 - D - 赖氨酸 - 苯丙氨酸 - O(Org 2766)。综述的第一部分着重于来自动物药理学、基础研究和人体研究的数据,这些数据与痴呆患者所显示的临床疗效相关。第二部分涉及人体临床研究。展示了一项针对156例原发性退行性痴呆(PDSD)患者使用Org 2766进行治疗的安慰剂对照剂量探索研究的自身结果。在该研究中发现,Org 2766对主要基于简易认知评定量表(SCAG)总分衡量的PDSD患者具有显著治疗效果,尽管该效果相当小(SCAG总分平均提高4分)。事后分析表明,仅25%的患者在临床上有相关疗效。对SCAG因子得分的分析表明对认知功能和躯体功能有影响。该研究未能显示出明确的剂量 - 反应关系。然而,在得出关于Org 2766疗效的最终结论之前,其结果必须得到其他研究的证实。

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