Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities

ABSTRACT

Introduction

Gastroparesis (Gp) and related disorders such as chronic unexplained nausea and vomiting and functional dyspepsia, known as gastropareis syndromes (GpS), have large unmet needs. Mainstays of GpS treatments are diet and drugs.

Areas Covered

The purpose of this review is to explore potential new medications and other therapies for gastroparesis. Before discussing possible new drugs, the currently used drugs are discussed. These include dopamine receptor antagonists, 5-hydroxytryptamine receptor agonists and antagonists, neurokinin-1 receptor antagonists and other anti-emetics. The article also considers future drugs that may be used for Gp, based on currently known pathophysiology.

Expert opinion

Gaps in knowledge about the pathophysiology of gastroparesis and related syndromes are critical to developing therapeutic agents that will be successful. Recent major developments in the gastroparesis arena are related to microscopic anatomy, cellular function, and pathophysiology. The major challenges moving forward will be to develop the genetic and biochemical correlates of these major developments in gastroparesis research.

KEYWORDS:

• Gastroparesis
• nausea
• vomiting
• functional dyspepsia
• medications

Article highlights

• Gastroparesis (Gp) is a chronic medical condition with an increasing disease burden and high morbidity and mortality.

• Gastroparesis like syndrome (GpS) includes patients with classical gastroparesis along with chronic unexplained nausea and vomiting and functional dyspepsia.

• The mainstays of treatment for GpS include dietary modifications and medications, although other treatments, such as bio-electrical stimulation and pyloric therapies, are increasingly being utilized.

• Several investigational therapies, such as new dopamine receptor agonists and antagonists, tetrahydrobiopterin (BH4) compounds, and motilin receptor agonists have been studied.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to thank Catherine McBride for help with manuscript preparation.

Declaration of interest

T Abell declares: Main funding from NIH GpCRC and Gastric Dysrhythmias; investigator for Censa, Cindome, Vanda, Allergan, Neurogastrx; consultant for Censa, Nuvaira, Takeda, Medtronic; speaker for Takeda. Medtronic; reviewer for UpToDate; GES Editor for Neuromodulation, WikiStim; ADEPT-GI IP for autonomic/enteric and bioelectric diagnosis and therapies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer declares: lecture fees from Takeda, AstraZeneca, EA Pharma, Daiich Sankyo, Otsuka. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

L Naing: Concept, literature survey, writing, final manuscript review. M Heckroth: Concept, literature survey, writing, final manuscript review. P Mathur: Concept, literature survey, writing, final manuscript review. T Abell: Concept, literature survey, writing, final manuscript review. All authors agree fpr the final version of the manuscript to be published.

Additional information

Funding

This paper was not funded.