NMDA Antagonists as Potential Analgesic Drugs

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.