Sensitivity to ivermectin and pyrantel of Ancylostoma ceylanicum and Necator americanus

Behnke, Jerzy M.; Rose, Richard A.; Garside, Paul

doi:10.1016/0020-7519(93)90061-3

Cited by 29 publications

(25 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies by Rajasekeriah et al (1989) also reported the relative insensitivity of N. americanus to IVM in the hamster model. The results of the above in vitro experiments in which the effects of IVM and pyrantel on motility were assessed support the results of these previous in vivo experiments (Behnke et al, 1993;Rajasekeriah et al, 1989) as A. ceylanicum and N. americanus were shown to have similar sensitivities to pyrantel, whereas A. ceylanicum was found to be approximately 50 times more sensitive to IVM (t = 3 h) than N. americanus. The difference in responsiveness to IVM does not appear to be related to response time as concentrations of IVM-PO4 that immobilized A. ceylunicum in 3 h (1.14 pm, 50% worms immobilized) had no detectable effect on N. americanus over 24 h.…”

Section: Discussionsupporting

confidence: 85%

“…Previous studies (Behnke et al, 1993) showed that in the hamster host, A. ceylanicum was on average 300 times more sensitive to IVM than N. americanus. Studies by Rajasekeriah et al (1989) also reported the relative insensitivity of N. americanus to IVM in the hamster model.…”

Section: Discussionmentioning

confidence: 94%

“…In vivo studies on hookworm infections in hamsters revealed that Ancylostoma ceylanicum was 300 times more sensitive to IVM than Necator americanus (Behnke, Rose & Garside, 1993). Previous work (Rajasekeriah, Deb, Dhage & Rose, 1989) also *To whom correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In vitro studies on the relative sensitivity to ivermectin of Necator americanus and Ancylostoma ceylanicum

Richards

Behnke

Duce

1995

International Journal for Parasitology

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

In vitro studies on the relative sensitivity to ivermectin of Necator americanus and Ancylostoma ceylanicum

Richards

Behnke

Duce

1995

International Journal for Parasitology

View full text Add to dashboard Cite

“…Unlike in C. elegans or C. oncophora (Cully et al, 1994;Njue et al, 2004), we could find no evidence of channels formed by, or incorporating, the GluCl␤ subunit of H. contortus. This suggests that the GluCl of different nematode species are rather different, supporting observations that ivermectin has varying effects on nematodes (Behnke et al, 1993;Sheriff et al, 2002;Holden-Dye and Walker, 2006). One factor contributing to the difference between the C. elegans and H. contortus GluCl␣3B channels might be that the amino acid residue at position 256 in C. elegans is phenylalanine rather than leucine, and the L256F change has been associated with resistance in C. oncophora.…”

Section: Discussionsupporting

confidence: 58%

An Ivermectin-Sensitive Glutamate-Gated Chloride Channel from the Parasitic Nematode Haemonchus contortus

McCavera

Rogers²,

Yates³

et al. 2009

Mol Pharmacol

119

View full text Add to dashboard Cite

Nematode glutamate-gated chloride channels are targets of the macrocyclic lactones, the most important group of anthelmintics available. In Xenopus laevis oocytes, channels formed by the GluCl␣3B subunit from the parasite Haemonchus contortus were more sensitive to L-glutamate (EC 50 ϭ 27.6 Ϯ 2.7 M) than those formed by the homologous subunit from Caenorhabditis elegans (EC 50 ϭ 2.2 Ϯ 0.12 mM). Ibotenate was a partial agonist (EC 50 ϭ 87.7 Ϯ 3.5 M). The H. contortus channels responded to low concentrations of ivermectin (estimated EC 50 ϭ ϳ0.1 Ϯ 1.0 nM), opening slowly and irreversibly in a highly cooperative manner: the rate of channel opening was concentration-dependent. Responses to glutamate and ivermectin were inhibited by picrotoxinin and fipronil. Mutating an N-terminal domain amino acid, leucine 256, to phenylalanine increased the EC 50 for L-glutamate to 92.2 Ϯ 3.5 M, and reduced the Hill number from 1.89 Ϯ 0.35 to 1.09 Ϯ 0.16. It increased the K d for radiolabeled ivermectin binding from 0.35 Ϯ 0.1 to 2.26 Ϯ 0.78 nM. Two other mutations (E114G and V235A) had no effect on L-glutamate activation or ivermectin binding: one (T300S) produced no detectable channel activity, but ivermectin binding was similar to wild-type. The substitution of any aromatic amino acid for Leu256 had similar effects in the radioligand binding assay. Molecular modeling studies suggested that the GluCl subunits have a fold similar to that of other Cys-loop ligand-gated ion channels and that amino acid 256 was unlikely to play a direct role in ligand binding but may be involved in mediating the allosteric properties of the receptor.

show abstract

“…Multiple studies investigating hookworm susceptibility to anthelmintics have reported that lower drug concentrations are effective against A. ceylanicum compared with N. americanus. 7,[38][39][40] These observations are supported by our comparative studies of the half-maximal inhibitory concentration (IC 50 ) values for ABZ and pyrantel pamoate (Table 4). For both compounds, higher IC 50 values were recorded for field isolates of hookworm compared with A. ceylanicum.…”

supporting

confidence: 71%

In vitro Screening of Compounds against Laboratory and Field Isolates of Human Hookworm Reveals Quantitative Differences in Anthelmintic Susceptibility

Treger

Otchere

Keil

et al. 2014

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. A panel of 80 compounds was screened for anthelmintic activity against a laboratory strain of Ancylostoma ceylanicum and field isolates of hookworm obtained from school children in the Kintampo North District of the Brong Ahafo Region of Ghana. Although the laboratory strain of A. ceylanicum was more susceptible to the compounds tested than the field isolates of hookworm, a twofold increase in compound concentration resulted in comparable egg hatch percent inhibition for select compounds. These data provide evidence that the efficacy of anthelmintic compounds may be species-dependent and that field and laboratory strains of hookworm differ in their sensitivities to the anthelmintics tested. These data also suggest that both compound concentration and hookworm species must be considered when screening to identify novel anthelmintic compounds.Human hookworm disease results from infection by two genera of hookworms, Ancylostoma spp. and Necator americanus. Albendazole (ABZ) and mebendazole (MBZ) are the primary drugs used to treat hookworm infection. A recent meta-analysis and review of field-based studies have shown that single-dose treatment cure rates with ABZ and MBZ are low (72% and 15%, respectively).1,2 Compounding these treatment failure rates in humans is the well-documented emergence of drug resistance to ABZ and MBZ among parasitic nematodes of agricultural and veterinary importance. [3][4][5] In light of this information, the development of novel anthelmintic chemotherapeutics is necessary.Currently, the identification and development of novel anthelmintic compounds to cure hookworm infection rely on laboratory-based screening for inhibitors of egg hatching, larval motility and morphology, and/or adult worm survival.6-9 However, novel compounds identified using small animal models of hookworm infection are rarely screened for comparable activity against field isolates of human hookworms. [10][11][12][13][14][15][16] Therefore, the correlation between the anthelmintic activity of compounds against laboratory and field isolates of human hookworms remains largely unknown.Moreover, for those cases in which anthelmintic activity is investigated, the larvicidal, rather than ovicidal, properties of a compound are usually analyzed. [17][18][19][20] Ovicidal activity is more frequently and most readily assayed in resource-limited field settings, where larval and adult hookworm-based assays are impractical tools for assessing anthelmintic activity. [21][22][23]

show abstract

Sensitivity to ivermectin and pyrantel of Ancylostoma ceylanicum and Necator americanus

Cited by 29 publications

References 21 publications

In vitro studies on the relative sensitivity to ivermectin of Necator americanus and Ancylostoma ceylanicum

In vitro studies on the relative sensitivity to ivermectin of Necator americanus and Ancylostoma ceylanicum

An Ivermectin-Sensitive Glutamate-Gated Chloride Channel from the Parasitic Nematode Haemonchus contortus

In vitro Screening of Compounds against Laboratory and Field Isolates of Human Hookworm Reveals Quantitative Differences in Anthelmintic Susceptibility

Contact Info

Product

Resources

About