Potential insight for drug discovery from high-fidelity receptor-mediated transduction mechanisms in insects

Abstract

Introduction: There is a pervasive and growing concern about the small number of new pharmaceutical agents. There are many proposed explanations for this trend that do not involve the drug-discovery process per se, but the discovery process itself has also come under scrutiny. If the current paradigms are indeed not working, where are novel ideas to come from? Perhaps it is time to look to novel sources.

Areas covered: The receptor-signaling and second-messenger transduction processes present in insects are quite similar to those in mammals (involving G proteins, ion channels, etc.). However, a review of these systems reveals an unprecedented degree of high potency and receptor selectivity to an extent greater than that modeled in most current drug-discovery approaches.

Expert opinion: A better understanding of insect receptor pharmacology could stimulate novel theoretical and practical ideas in mammalian pharmacology (drug discovery) and, conversely, the application of pharmacology and medicinal chemistry principles could stimulate novel advances in entomology (safer and more targeted control of pest species).

Keywords:

• drug discovery
• insects
• pheromones
• receptors
• second-messengers
• therapeutic targets

Acknowledgements

Critical reviews of various aspects of the manuscript by RJ Tallarida (Department of Pharmacology, Temple University School of Medicine), RT Cardé (Department of Entomology, University of California-Riverside), J Frazier (Department of Entomology, Pennsylvania State University) and P Tobin (USDA-FS) improved this manuscript and are greatly appreciated.

Notes

This box summarizes key points contained in the article.