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Prospects for rational approaches to anthelmintic discovery

Published online by Cambridge University Press:  06 April 2009

D. P. Thompson ,
R. D. Klein  and
T. G. Geary
D. P. Thompson*
Affiliation:
Animal Health Discovery Research, Mailstop 7923-25-13, Pharmacia & Upjohn, Co., 301 Henrietta Street, Kalamazoo, MI 49001, USA
R. D. Klein
Affiliation:
Animal Health Discovery Research, Mailstop 7923-25-13, Pharmacia & Upjohn, Co., 301 Henrietta Street, Kalamazoo, MI 49001, USA
T. G. Geary
Affiliation:
Animal Health Discovery Research, Mailstop 7923-25-13, Pharmacia & Upjohn, Co., 301 Henrietta Street, Kalamazoo, MI 49001, USA
*
*Corresponding author.
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Summary

Rational approaches to anthelmintic discovery include the design of screens for compounds directed at specific proteins in helminths that are pharmacologically distinguishable from their vertebrate homologues. The existence of several anthelmintics that selectively target the neuromusculature of helminths (e.g. levamisole, ivermectin, praziquantel, metrifonate), together with recent basic research in helminth physiology, have contributed to the recognition that neurobiology distinguishes these organisms from their vertebrate hosts. In this survey, we focus on mechanism-based screening and its application to anthelmintic discovery, with particular emphasis on targets in the neuromusculature of helminths. Few of these proteins have been exploited in chemotherapy. However, recent studies in comparative pharmacology and molecular biology, including the C. elegans genome project, have provided insights on potential new targets and, in some cases, molecular probes useful for their incorporation in mechanism-based screens.

Keywords

Rational drug discoverymechanism-based screenshigh-throughput screenscomparative neuropharmacologyneuroreceptorsnutrient-dependent viability assay

Information

Type
Research Article
Information
Parasitology , Volume 113 , supplement S1: Molecular biochemistry and physiology of helminth neuromuscular systems , January 1996 , pp. S217 - S238
Copyright
Copyright © Cambridge University Press 1996

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