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In the prokinetic arena, the void left by the withdrawal from the market of cisapride has yet to be filled. There is still some confusion over whether the beneficial prokinetic effects of cisapride resulted wholly from activity at the 5HT4 receptor and only the successful development of a selective 5HT4 receptor agonist will allow that question to be fully answered. Since the withdrawal of cisapride, the treatment of GERD has been refined, with proton pump inhibitors becoming the standard of care. These drugs offer high levels of symptom relief in many patients and thus the clinical usefulness of the next generation of prokinetic drugs will need to be established within this context. The projected rise in the number of patients with diabetes suggests that diabetic gastroparesis could also substantially increase, offering another opportunity for prokinetic agents to bring benefit to patients (see 6.19 Diabetes/Syndrome X).

In the area of antiemetic therapy, the challenge is to develop agents with which to better control nausea. This will almost certainly depend upon the future development of reliable and predictive animal models in which to map the nausea pathways of the CNS and in which to ultimately understand the potential of novel antinausea medications.


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Jeremy D Gale is a drug developer with 17 years experience in major R&D-based pharmaceutical companies working across the continuum of drug discovery and development. He graduated in pharmacology and then completed a PhD in pharmacology and neuroscience at the University of London. He joined Glaxo in 1988 and for almost 8 years worked in gastrointestinal pharmacology, leading the biology teams that formed part of the irritable bowel syndrome (IBS) and emesis research programes. Jeremy joined Pfizer in 1995 to lead the biology research team focused on gastroenterological diseases, developing expertise in IBS, inflammatory bowel disease (IBD), and gastroesophageal reflux disease (GERD). In 2002, he moved into Exploratory Clinical Development, becoming clinical leader for programs targeting GERD and IBD. In addition, Jeremy leads translational medicine activities and biomarker development for the gastroenterology and hepatology therapeutic area.


Ichiro Mori received an MA from Kyoto University (Prof H Nozaki), then his PhD from University of California, Berkeley in 1988 (Professors P A Bartlett and C H Heathcock) on development of stereoselective chemistry-related aldol reactions. In 1998, he spent 1 year at the Massachusetts Institute of Technology as a postdoctoral fellow with Professor R L Danheiser to investigate new synthetic methods of indols, and joined Ciba-Geigy Japan to develop inhibitors of histidine biosynthesis as herbicides. He then joined Glaxo Japan in 1997, working on the synthesis of kinase inhibitors. In 2003, he moved to Pfizer and is currently working on medicinal chemistry in the gastroenterology and hepatology therapeutic area.

© 2007 Elsevier Ltd. All Rights Reserved Comprehensive Medicinal Chemistry II

No part of this publication may be reproduced, stored in any retrieval system or transmitted ISBN (set): 0-08-044513-6 in any form by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers ISBN (Volume 6) 0-08-044519-5; pp. 671-691

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