Structure-activity relationship of vasoactive intestinal peptide (VIP): potent agonists and potential clinical applications

被引:0
作者
Satomi Onoue
Shingen Misaka
Shizuo Yamada
机构
[1] University of Shizuoka,Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences
来源
Naunyn-Schmiedeberg's Archives of Pharmacology | 2008年 / 377卷
关键词
VIP; PAC1; VPAC1; VPAC2; Structure–activity relationship; DDS;
D O I
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中图分类号
学科分类号
摘要
Vasoactive intestinal peptide (VIP) has been identified as one of major peptide transmitters in the central and peripheral nervous systems, being involved in a wide range of biological functions. The general physiologic effects of VIP include vasodilation, anti-inflammatory actions, cell proliferation, hormonal secretion, regulation of gastric motility, and smooth muscle relaxation; therefore, VIP has emerged as a promising drug candidate for the treatment of several diseases. A number of clinical applications of VIP or its derivatives have been developed; however, VIP-based drugs are not yet in clinical use, possibly because of mainly two serious problems: (1) poor metabolic stability and (2) poor penetration to the desired site of action. To overcome these shortcomings, the development of efficacious VIP analogues and several drug delivery systems has been attempted on the basis of numerous structure–activity relationships (SAR) studies and pharmacological experiments. Combination of the use of potent VIP analogues and an appropriate drug delivery system might be advantageous for the VIP-based therapy. We review in this paper SAR studies of VIP for the identification of potent therapeutic agents, describe the development of selective and/or metabolically stable VIP receptor agonists/antagonists, and discuss the potential application for clinical treatment using drug delivery systems.
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页码:579 / 590
页数:11
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