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Dalip J. S. Sirinathsinghii and Ray G. Hill Merck, Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK There remains a distinct medical need for new pain therapies. Therefore, it is not surprising that in recent years there has been a major research initiative in both aca demic and pharmaceutical laboratories to identify novel pain targets and to devel op novel analgesic drugs. It is clear from numerous studies that the NMDA recep tor plays a major role in the transmission ofnociceptive information and it has been a subject of extensive investigation over the last decade exploiting the advances of molecular pharmacology and molecular neuroanatomy. As a consequence there has been a rational approach by several laboratories to develop receptor subtype-spe cific NMDA antagonists in order to avoid the wide range of side-effects seen with non-selective NMDA ion channel antagonists such as ketamine. This volume brings together contributions from experts in various technological disciplines who have contributed immensely to NMDA receptor research and advanced our understanding of the subunit composition of the NMDA receptor complex, its pharmacology and distribution, its interaction with other neurochemi cal systems and the effects on behaviour of NMDA antagonists in rodent models and in the clinic. In consideration of these advances and the prospects of novel NMDA receptor antagonists in the near future for the treatment of pain, this vol ume is very timely.
List of contents
Pharmacology and electrophysiology of excitatory amino acid receptors.- Distribution of NMDA receptors in brain and spinal cord.- Spinal nociceptive processing: NMDA receptors and modulation by neuropeptides.- The NMDA receptor, pain and central sensitization.- Some pharmacological aspects of NMDA-mediated nociceptive transmission in the rat spinal cord as revealed by c-fos immunocytochemistry.- Interaction of NMDA and other neurotransmitter receptor systems in modulation of nociception.- Behavioural studies on the potential of NMDA receptor antagonists as analgesics.- Clinically available glutamate receptor antagonists in neuropathic pain states.- Future prospects for improved analgesic therapy.
Summary
There is now considerable preclinical evidence that glutamate acting via
the NMDA receptor is involved in the transmission of nociceptive
information and in the triggering mechanisms for hyperalgesia and
allodynia. This evidence allows rational development of a new class of
analgesic drugs that act as antagonists of the NMDA receptor, supported
by emerging evidence with existing excitatory amino acid antagonists.
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