Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions
The rationale for using thalidomide (THD) as a treatment for nausea and vomiting during pregnancy in the late 1950s appears to have been based on its sedative or hypnotic properties. In contrast to contemporaneous studies on the anti-emetic activity of phenothiazines, we were unable to identify publ...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Current Research in Pharmacology and Drug Discovery |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S259025712200058X |
| _version_ | 1828091619271770112 |
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| author | Paul L.R. Andrews Robin S.B. Williams Gareth J. Sanger |
| author_facet | Paul L.R. Andrews Robin S.B. Williams Gareth J. Sanger |
| author_sort | Paul L.R. Andrews |
| collection | DOAJ |
| description | The rationale for using thalidomide (THD) as a treatment for nausea and vomiting during pregnancy in the late 1950s appears to have been based on its sedative or hypnotic properties. In contrast to contemporaneous studies on the anti-emetic activity of phenothiazines, we were unable to identify publications reporting preclinical or clinical evaluation of THD as an anti-emetic. Our survey of the literature revealed a clinical study in 1965 showing THD reduced vomiting in cancer chemotherapy which was substantiated by similar studies from 2000, particularly showing efficacy in the delayed phase of chemotherapy-induced nausea and vomiting. To identify the mechanism(s) potentially involved in thalidomide's anti-emetic activity we reviewed its pharmacology in the light of nausea and vomiting mechanisms and their pharmacology with a particular emphasis on chemotherapy and pregnancy. The process identified the following potential mechanisms: reduced secretion of Growth Differentiation Factor 15, suppression of inflammation/prostaglandin production, downregulation of cytotoxic drug induced upregulation of iNOS, and modulation of BK (KCa1.1) channels and GABAA/glutamate transmission at critical points in the emetic pathways (nucleus tractus solitarius, area postrema). We propose ways to investigate these hypothesized mechanisms and discuss the associated challenges (e.g., objective quantification of nausea) in addition to some of the more general aspects of developing novel drugs to treat nausea and vomiting. |
| first_indexed | 2024-04-11T06:15:51Z |
| format | Article |
| id | doaj.art-f182818659954f80941417ac2bfc0d24 |
| institution | Directory Open Access Journal |
| issn | 2590-2571 |
| language | English |
| last_indexed | 2024-04-11T06:15:51Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Pharmacology and Drug Discovery |
| spelling | doaj.art-f182818659954f80941417ac2bfc0d242022-12-22T04:41:04ZengElsevierCurrent Research in Pharmacology and Drug Discovery2590-25712022-01-013100138Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directionsPaul L.R. Andrews0Robin S.B. Williams1Gareth J. Sanger2Division of Biomedical Sciences, St George's University of London, London, United Kingdom; Corresponding author.Centre for Biomedical Sciences, Department of Biological Sciences, Royal Holloway University of London, Egham, United KingdomBlizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, United KingdomThe rationale for using thalidomide (THD) as a treatment for nausea and vomiting during pregnancy in the late 1950s appears to have been based on its sedative or hypnotic properties. In contrast to contemporaneous studies on the anti-emetic activity of phenothiazines, we were unable to identify publications reporting preclinical or clinical evaluation of THD as an anti-emetic. Our survey of the literature revealed a clinical study in 1965 showing THD reduced vomiting in cancer chemotherapy which was substantiated by similar studies from 2000, particularly showing efficacy in the delayed phase of chemotherapy-induced nausea and vomiting. To identify the mechanism(s) potentially involved in thalidomide's anti-emetic activity we reviewed its pharmacology in the light of nausea and vomiting mechanisms and their pharmacology with a particular emphasis on chemotherapy and pregnancy. The process identified the following potential mechanisms: reduced secretion of Growth Differentiation Factor 15, suppression of inflammation/prostaglandin production, downregulation of cytotoxic drug induced upregulation of iNOS, and modulation of BK (KCa1.1) channels and GABAA/glutamate transmission at critical points in the emetic pathways (nucleus tractus solitarius, area postrema). We propose ways to investigate these hypothesized mechanisms and discuss the associated challenges (e.g., objective quantification of nausea) in addition to some of the more general aspects of developing novel drugs to treat nausea and vomiting.http://www.sciencedirect.com/science/article/pii/S259025712200058XChemotherapyGDF15Hyperemesis gravidarumNauseaThalidomideVomiting |
| spellingShingle | Paul L.R. Andrews Robin S.B. Williams Gareth J. Sanger Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions Current Research in Pharmacology and Drug Discovery Chemotherapy GDF15 Hyperemesis gravidarum Nausea Thalidomide Vomiting |
| title | Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions |
| title_full | Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions |
| title_fullStr | Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions |
| title_full_unstemmed | Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions |
| title_short | Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions |
| title_sort | anti emetic effects of thalidomide evidence mechanism of action and future directions |
| topic | Chemotherapy GDF15 Hyperemesis gravidarum Nausea Thalidomide Vomiting |
| url | http://www.sciencedirect.com/science/article/pii/S259025712200058X |
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