THE PHARMACOLOGY OF FMRFAMIDE-RELATED NEUROPEPTIDES IN NEMATODES - NEW OPPORTUNITIES FOR RATIONAL ANTHELMINTIC DISCOVERY

The chemotherapeutic control of helminth parasites is compromised by t he limited number of classes of anthelmintic drugs. Discovery of novel anthelmintics is impeded by the lack of novel screening technologies that overcome the difficulties inherent in screens based on whole orga nism toxicity. The development and implementation of mechanism-based s creens for new anthelmintics offers great promise for the revitalizati on of antiparasitic drug discovery. However, mechanism-based screens m ust be based on a thorough understanding of the proteins or processes that offer the best chance for selective chemotherapeutic intervention . Basic research on the characterization of nematode FMRF amide-relate d peptides (FaRPs) has revealed that these peptides are ubiquitously d istributed in helminths. Chemical identification of a number of nemato de FaRPs has been achieved, and these peptides have potent and profoun d effects on the nematode neuromuscular system. Physiological processe s mediated by nematode FaRPs (and other helminth neuropeptides) offer potential targets for the discovery of novel anthelmintics.