ABSTRACT
With l-glutamate being the major excitatory neurotransmitter in the central nervous system (CNS), glutamate receptors have inescapably been the focus of interest as central targets for analgesia. The longer history and better understanding of the function and role of receptors for N-methyl-d-aspartate (NMDA) are explained by early discoveries of selective agonists and antagonists in pioneering studies by Watkins and colleagues (for review see Ref. 1). The initial expectations of a quick route for NMDA antagonists into the pain clinic were followed by a tide of disappointment resulting from a palette of specific side effects. In this chapter we describe some current approaches to the development of new analgesics based on recent advances in the understanding of the NMDA receptor complex. Given the very large literature on this topic, it has not been possible for us within the scope of this short review to embrace all aspects or to cite more than a small selection of the relevant references; reviews are cited where possible.
