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Drug resistance and neurotransmitter receptors of nematodes: recent studies on the mode of action of levamisole

Published online by Cambridge University Press:  29 March 2006

R. J. MARTIN ,
S. VERMA ,
M. LEVANDOSKI ,
C. L. CLARK ,
H. QIAN ,
M. STEWART  and
A. P. ROBERTSON
R. J. MARTIN
Affiliation:
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA
S. VERMA
Affiliation:
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA
M. LEVANDOSKI
Affiliation:
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA
C. L. CLARK
Affiliation:
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA
H. QIAN
Affiliation:
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA
M. STEWART
Affiliation:
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA
A. P. ROBERTSON
Affiliation:
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA
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Abstract

Here we review recent studies on the mode of action of the cholinergic anthelmintics (levamisole, pyrantel etc.). We also include material from studies on the free living nematode Caenorhabditis elegans. The initial notion that these drugs act on a single receptor population, while attractive, has proven to be an oversimplification. In both free living and parasitic nematodes there are multiple types of nicotinic acetylcholine receptor (nAChR) on the somatic musculature. Each type has different (sometimes subtly so) pharmacological properties. The implications of these findings are: (1) combinations of anthelmintic that preferentially activate a broad range of nAChR types would be predicted to be more effective; (2) in resistant isolates of parasite where a subtype has been lost, other cholinergic anthelmintics may remain effective. Not only are there multiple types of nAChR, but relatively recent research has shown these receptors can be modulated; it is possible to increase the response of a parasite to a fixed concentration of drug by altering the receptor properties (e.g. phosphorylation state). These findings offer a potential means of increasing efficacy of existing compounds as an alternative to the costly and time consuming development of new anthelmintic agents.

Keywords

nAChRlevamisoleresistancereceptor modulationreceptor subtype
Type
Research Article
Information
Parasitology , Volume 131 , Supplement S1: Parasite neuromusculature and its utility as a drug target , October 2005 , pp. S71 - S84
Copyright
2005 Cambridge University Press

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