title: Anthelmintics: The best way to predict the future is to create it.
abstract: 'The best way to predict the future is to create it.' When we look at drugs that are used to control parasites, we see that new knowledge has been created (discovered) about their modes of action. This knowledge will allow us to predict combinations of drugs which can be used together rationally to increase the spectrum of action and to slow the development of anthelmintic resistance. In this paper we comment on some recent observations of ours on the modes of action of emodepside, diethylcarbamazine and tribendimidine. Emodepside increases the activation of a SLO-1 K(+) current inhibiting movement, and diethylcarbamazine has a synergistic effect on the effect of emodepside on the SLO-1 K(+) current, increasing the size of the response. The combination may be considered for further testing for therapeutic use. Tribendimidine is a selective cholinergic nematode B-subtype nAChR agonist, producing muscle depolarization and contraction. It has different subtype selectivity to levamisole and may be effective in the presence of some types of levamisole resistance. The new information about the modes of action may aid the design of rational drug combinations designed to slow the development of resistance or increase the spectrum of action.
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA. Electronic address: rjmartin@iastate.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Verma
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors.forename: Shivani
authors.initials: S
authors.lastname: Choudhary
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors.forename: Sudhanva
authors.initials: S
authors.lastname: Kashyap
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Abongwa
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors.forename: Fudan
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Robertson
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology* / Q000627:therapeutic use*; D047630:Depsipeptides / Q000494:pharmacology / Q000627:therapeutic use; D004049:Diethylcarbamazine / Q000494:pharmacology / Q000627:therapeutic use; D006376:Helminths / Q000187:drug effects; D010273:Parasitic Diseases, Animal / Q000188:drug therapy*; D010655:Phenylenediamines / Q000494:pharmacology / Q000627:therapeutic use; D019155:Veterinary Drugs / Q000494:pharmacology / Q000627:therapeutic use; D014730:Veterinary Medicine / Q000639:trends*
chemical_list: D000871:Anthelmintics; D047630:Depsipeptides; D010655:Phenylenediamines; D019155:Veterinary Drugs; C056017:tribendimidine; D004049:Diethylcarbamazine; C468987:emodepside
keywords: Anthelmintic; Diethylcarbamazine; Emodepside; Mode of action; Tribendimidine