Gr79236

6.16.7.4 Adenosine

Adenosine antagonists decreased nociceptive thresholds in rats.80 The antinociceptive effects of adenosine are mediated via the A1 receptor.81'82 This has been localized in human trigeminal ganglia,83 suggesting a potential ability of adenosine A1 receptor agonists to inhibit the trigeminal nerve. Selective adenosine A1 receptor agonists, e.g., GR-79236, 11, can inhibit trigeminovascular activation, both in the trigeminal nucleus and by inhibition of release of CGRP in the cranial circulation.84 The effect within the trigeminal nucleus reflects a central action, whilst inhibition of CGRP release is likely to be attributable to an action at adenosine A1 receptors on peripheral terminals of the trigeminal nerve. Both effects are in keeping with the concept of adenosine A1 receptors being located prejunctionally on primary afferent neurons and causing inhibition of transmitter release. Adenosine A1 receptor agonists, such as GR-79236, have no effect on resting meningeal artery diameter in rats.85 Moreover, GR-79236 can inhibit the nociceptive trigeminal blink reflex at doses in humans52 that are both trigeminally inhibitory and without vascular effects in experimental animals.

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Biography

Peter J Goadsby obtained his basic medical degree and training at the University of New South Wales, Australia. His neurology training was done under the supervision of Prof James Lance in Sydney. After postdoctoral work in New York with Don Reis at Cornell, with Jacques Seylaz in Paris, and postgraduate neurology training at Queen Square in London, he returned to the University of New South Wales, and the Prince of Wales Hospital, Sydney as a consultant neurologist and, in 1994 as associate professor of neurology.

He was appointed a Wellcome Senior Research Fellow at the Institute of Neurology, University College London in 1995. He is currently professor of clinical neurology and consultant neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square, and the Hospital for Sick Children, Great Ormond St., London. His major research interests are in the neural control of the cerebral circulation and the basic mechanisms of head pain in both experimental settings and in the clinical context of headache. The work of the Headache Group involves human imaging and electrophysiological studies in primary headache, as well as experimental studies of trigeminovascular nociception. We aim to understand what parts of the brain drive and modulate headache syndromes, and how those might be modified by treatment.

© 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. 369-379

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