title: Phenotypic assessment of the ovicidal activity of monepantel and monepantel sulfone on gastro-intestinal nematode eggs.
abstract: The in vitro ovicidal activity of the amino acetonitrile derivative, monepantel (MPTL) and its active metabolite monepantel sulfone (MPTL-SO2) were assessed against a number of commercially important nematode species of ruminants, namely Teladorsagia circumcincta, Haemonchus contortus and Trichostrongylus axei. An egg hatch test (EHT) was used to make the assessment of both drug sensitive and drug resistant isolates. Both MPTL and MPTL-SO2 showed moderate ovicidal activity in vitro against all of the species examined, although species specific differences as measured by inhibitory concentration were observed. Analysis of the drug sensitive isolates showed H. contortus to be the most sensitive to both MPTL and MPTL-SO2 (ED50 1.7 and 2.7 μg/ml respectively) followed by T. circumcincta (ED50 2.1 and 2.7 μg/ml respectively) followed by T. axei (ED50 68.7 and 60.1 μg/ml respectively). Overall the EHT results would suggest no "global" in vitro discriminatory dose for detection of MPTL resistance is likely to be achievable, using the egg hatch test, due to large inherent variability observed between species. The test identified a dose dependent increase in MPTL and MPTL-SO2 sensitivity in two MPTL resistant T. circumcincta isolates and therefore offers to be a promising tool for the phenotypic characterisation of MPTL sensitivity, allowing exploration into the mechanisms involved in selection and development of MPTL resistance.
authors.affiliation: Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, United Kingdom. Electronic address: dave.bartley@moredun.ac.uk.
authors.forename: D J
authors.initials: DJ
authors.lastname: Bartley
authors.affiliation: Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, United Kingdom. Electronic address: margaux.mesle@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Meslé
authors.affiliation: Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, United Kingdom. Electronic address: hcdonegan@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Donegan
authors.affiliation: Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, United Kingdom. Electronic address: leigh.devin@moredun.ac.uk.
authors.forename: L
authors.initials: L
authors.lastname: Devin
authors.affiliation: Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, United Kingdom. Electronic address: alison.morrison@moredun.ac.uk.
authors.forename: A A
authors.initials: AA
authors.lastname: Morrison
mesh_terms: D000607:Aminoacetonitrile / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D004351:Drug Resistance; D004625:Embryo, Nonmammalian / Q000187:drug effects; D006189:Haemonchus / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D010641:Phenotype; D013450:Sulfones / Q000494:pharmacology*; D014254:Trichostrongylus / Q000187:drug effects*; D015053:Zygote / Q000187:drug effects
chemical_list: D000871:Anthelmintics; D013450:Sulfones; C553923:monepantel sulfone; D000607:Aminoacetonitrile; C533978:monepantel
keywords: Egg hatch; In vitro; Monepantel; Monepantel sulfone; Resistance; Teladorsagia circumcincta.