A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research

Frontiers in Pharmacology
Gareth J Sanger, Paul L R Andrews

Abstract

The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries have occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i) Muscarinic receptor antagonists-originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) Histamine receptor antagonists-searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H1) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists-investigations of their pharmacology as "sedatives" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D2) receptor antagonists (e.g., domperidone with poor ability to penetrate ...Continue Reading

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Citations

Feb 6, 2019·Future Oncology·Toni Leigh MortimerAnna-Mart Engelbrecht
May 23, 2019·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Gema VeraRaquel Abalo
Apr 5, 2020·Expert Review of Clinical Pharmacology·Gabriel Fox, Peter Kranke
May 30, 2020·British Journal of Hospital Medicine·Mansimran S Dulay, Jasbir S Dulay
Aug 8, 2019·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·Rita J Wickham
Sep 22, 2020·Journal of Gastroenterology and Hepatology·Paul L R AndrewsGareth J Sanger
Nov 28, 2020·Current Treatment Options in Oncology·Mellar P Davis, Gareth J Sanger
May 18, 2021·Frontiers in Pharmacology·W Zhong, N A Darmani
Jun 29, 2021·Diabetes·Matthew R HayesBart C De Jonghe

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Methods Mentioned

BETA
sedation
imaging techniques

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