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Cannabinoid Receptor Modulators

Cannabis has been used for centuries to treat GI pain. Cannabinoids appear to have a neuromodulator role in the GI system. CBl-cannabinoid receptors are present in the human ileum and colon, and their pharmacological activation leads to inhibition of excitatory cholinergic pathways involved in smooth-muscle contraction. Endogenous cannabinoids are physiological downregulators of colonic propulsion in mice; their actions on myenteric CBl-cannabinoid receptors leads to inhibition of colonic propulsion.203 In keeping with this, in a study in mice, the competitive cannabinoid receptor antagonist rimonabant 11 enhanced motor activity in colonic smooth muscle. Modulation of peripheral cannabinoid receptors could thus provide relief from both sensory and motor components of IBS symptoms.192

Rimonabant 11


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Gareth A Hicks has worked in the neuroscience field for over 15 years and in gastrointestinal research for the last eight of these. Following undergraduate studies in the Department of Pharmacology, University College London, Gareth trained as an electrophysiologist during doctoral and postdoctoral work in the Department of Pharmacology,

University of Cambridge, and the Vollum Institute in Portland, Oregon. After joining GlaxoWellcome (now GSK) in the UK in 1996, his research focus shifted to the gastrointestinal system, and irritable bowel syndrome in particular. Between that time and 2004, Gareth had various research and management roles, culminating in his appointment to the position of head of gastrointestinal research. From 2004 to the present, he has worked at Novartis Pharmaceuticals Corporation (New Jersey, USA) in the Medical Affairs Department of a multidisciplinary therapeutic area that covers gastrointestinal, urological, bone, and arthritic disease clinical development. Gareth's primary interest is understanding the pathophysiology of diseases, and the mechanisms of action of drugs used to treat them.

© 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. 643-670

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