Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain

被引：17

作者：

Brierley, Stuart M. ^{[1
,2
,3
]}

Grundy, Luke ^{[1
,2
]}

Castro, Joel ^{[1
,2
]}

Harrington, Andrea M. ^{[1
,2
]}

Hannig, Gerhard ^{[4
]}

Camilleri, Michael ^{[5
]}

机构：

[1] Flinders Univ S Australia, Flinders Hlth & Med Res Inst FHMRI, Coll Med & Publ Hlth, Visceral Pain Res Grp, Bedford Pk, SA 5042, Australia

[2] South Australian Hlth & Med Res Inst SAHMRI, Hopwood Ctr Neurobiol, Lifelong Hlth Theme, North Terrace, Adelaide, SA 5000, Australia

[3] Univ Adelaide, Discipline Med, North Terrace, Adelaide, SA 5000, Australia

[4] Ironwood Pharmaceut, Boston, MA USA

[5] Mayo Clin, Clin Enter Neurosci Translat & Epidemiol Res Prog, Rochester, MN USA

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2022年 / 43卷 / 02期

基金：

澳大利亚国家健康与医学研究理事会; 澳大利亚研究理事会; 英国医学研究理事会;

关键词：

IRRITABLE-BOWEL-SYNDROME; GASTROINTESTINAL-TRACT; CONTROLLED-TRIAL; ABDOMINAL-PAIN; LINACLOTIDE; EFFICACY; COLON; ACTIVATION; MOUSE; CONSTIPATION;

D O I：

10.1016/j.tips.2021.11.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habit that affects similar to 11% of the global population. Over the past decade, preclinical and clinical studies have revealed a variety of novel mechanisms relating to the visceral analgesic effects of guanylate cyclase-C (GC-C) agonists. Here we discuss the mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3 ',5 '-monophosphate (cGMP) pathway, resulting in visceral analgesia as well as clinically relevant relief of abdominal pain and other sensations in IBS patients. Due to the preponderance of evidence we focus on linaclotide, a 14-amino acid GC-C agonist with very low oral bioavailability that acts within the gut. Collectively, the weight of experimental and clinical evidence supports the concept that GC-C agonists act as peripherally acting visceral analgesics.

引用

页码：110 / 122

页数：13

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