From basic research on neuropeptide receptors to clinical benefit.
The present article provides a concise overview of progress in our understanding of neuropeptides, their receptors and the current and potential ways in which they may be targeted for clinical use. Neuropeptide systems offer certain characteristics that distinguish them from those utilizing classic neurotransmitters and thus make them increasingly attractive for drug targeting. A key example of the highly successful use of neuropeptide receptor ligands is that of opioid receptor agonists for the treatment of pain. More recently, classically identified neuropeptide receptors, including those for substance P, cholecystokinin and neurotensin, have been singled out for development of antagonists by several pharmaceutical companies, for various therapeutic indications. These examples can be categorized as having been identified using classic methods; that is, the neuropeptide(s) and/or their function(s) were established prior to molecular identification of their receptor(s). Modern methodologies being widely applied in the industry today have somewhat reversed the need for this ordering in drug discovery. Technologies based upon bioinformatics, molecular, proteomic and transgenic approaches have accelerated the identification of putative receptor targets and the generation of information on their involvement in physiological and pathophysiological processes. Now research and development teams are in a position to best select targets from this rapidly expanding catalogue. This article seeks to outline aspects of these procedures and additionally summarize recent data which have important implications for drug development in this field. Consideration has been given to potential targets and how these may ultimately lead to clinical benefit.
Oliver
K R
KR
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Sirinathsinghji
D J
DJ
Hill
R G
RG