In vitro and in vivo characterization of p-amino-phenethyl-m-trifluoromethylphenyl piperazine (PAPP), a novel serotonergic agonist with anthelmintic activity against Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis

White, W. Hunter; Gutiérrez, Julián; Naylor, Sharon A.; Cook, Carolyn A.; González, Isabel Chirivella; Wisehart, Mark A.; Smith, Charles Kent; Thompson, W. A.

doi:10.1016/j.vetpar.2007.02.014

Cited by 19 publications

(17 citation statements)

References 15 publications

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“…Due to the high standard error (4.4%) in Trial 2b, LV was similar at all PEG concentrations tested (0-2%, w/v; 89.4, 78.9, 76.5, 75.5, and 77.5% viable, respectively). The L3 larvae do not feed in the rumen (Gamble and Mansfield, 1996;White et al, 2007), thus larvae motility was probably not related to ingested PEG or CT. Future trials using this assay need to consider the effects of PEG on LMI.…”

Section: Trials 2a and 2bmentioning

confidence: 99%

A modified in vitro larvae migration inhibition assay using rumen fluid to evaluate Haemonchus contortus viability

Whitney¹,

Lee²,

Klein

et al. 2011

Veterinary Parasitology

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Section: Trials 2a and 2bmentioning

confidence: 99%

A modified in vitro larvae migration inhibition assay using rumen fluid to evaluate Haemonchus contortus viability

Whitney¹,

Lee²,

Klein

et al. 2011

Veterinary Parasitology

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“…All of these molecules act at GPCRs (Komuniecki et al, 2004), though, as stated earlier, nematodes also possess chloride channels gated by 5-HT, dopamine and tyramine. At least some of these receptors have also been identified in parasitic species (Huang et al, 1999(Huang et al, , 2002Smith et al, 2003Smith et al, , 2007 and many have distinct pharmacological characteristics that suggest that nematode-specific agonists and antagonists could be developed as useful anthelmintics (White et al, 2007). In C. elegans, dopamine and 5-HT have well-established roles in modulating behavior, including locomotion, feeding and egg-laying (Chase and Koelle, 2007).…”

Section: G Protein-coupled Receptorsmentioning

confidence: 99%

Ion channels and receptor as targets for the control of parasitic nematodes

Wolstenholme

2011

International Journal for Parasitology: Drugs and Drug Resistan

103

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Many of the anthelmintic drugs in use today act on the nematode nervous system. Ion channel targets have some obvious advantages. They tend to act quickly, which means that they will clear many infections rapidly. They produce very obvious effects on the worms, typically paralyzing them, and these effects are suitable for use in rapid and high-throughput assays. Many of the ion channels and enzymes targeted can also be incorporated into such assays. The macrocyclic lactones bind to an allosteric site on glutamate-gated chloride channels, either directly activating the channel or enhancing the effect of the normal agonist, glutamate. Many old and new anthelmintics, including tribendimidine and the amino-acetonitrile derivatives, act as agonists at nicotinic acetylcholine receptors; derquantel is an antagonist at these receptors. Nematodes express many different types of nicotinic receptor and this diversity means that they are likely to remain important targets for the foreseeable future. Emodepside may have multiple effects, affecting both a potassium channel and a pre-synaptic G protein-coupled receptor; although few other current drugs act at such targets, this example indicates that they may be more important in the future. The nematode nervous system contains many other ion channels and receptors that have not so far been exploited in worm control but which should be explored in the development of effective new compounds.

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“…Mongolian gerbil has also been recognized as a suitable to evaluate the efficacy of several natural substances with anthelmintic properties -tannins (Rojas et al, 2006), artemisine (Squires et al, 2011), orange oil emulsion (Squires et al, 2010) against the H. contortus infection. P-aminophenethyl-m-trifluoromethylphenyl piperazine (PAPP) has also found highly effective against co-infection of H. HELMINTHOLOGIA, 49, 4: 211 -220, 2012 Effect of albendazole therapy on susceptible and resistant Haemonchus contortus larvae in Mongolian gerbils (Meriones unguiculatus) and distribution of inflammatory cells in the stomach wall (White et al, 2007). The eosinophilia and mastocytosis are characteristic in mammals infected with gastrointestinal nematodes (Miller, 1984).…”

Section: Introductionmentioning

confidence: 99%

Effect of albendazole therapy on susceptible and resistant Haemonchus contortus larvae in Mongolian gerbils (Meriones unguiculatus) and distribution of inflammatory cells in the stomach wall

et al. 2012

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211 SummaryThe effect of albendazole therapy on the reduction of drugsusceptible and drug-resistant strains of Haemonchus contortus larvae on day 10 post infection (p.i.), distribution and the relative numbers of innate immunity cells -eosinophils/neutrophils and mast cells in the stomach wall of immunosupressed Mongolian gerbils on days 4/1, 7/4, 10/7 and 14/11 post infection/post therapy (p.i./p.t.) were investigated in the present study. The efficacy of albendazole was significantly lower on benzimidazole (BZ) resistant larvae (L3 and L4 stages) (58.92 %) than the efficacy on susceptible strain of larvae (94.15 %). H. contortus infection elicited strong inflammation in mucosal and submucosal layers of the stomach, where mucosal mast cells (MMC) were in the highest numbers in the lamina propria mucosae on day 7/4 p.i./p.t. Reduction of larval numbers following treatment resulted in a gradual decrease of MMC and connective tissue mast cells (CTMC). The lower counts of CTMC in the submucosa were seen in gerbils infected with BZ-susceptible strain during the whole period post therapy. In case of infection with BZ-resistant strain, peroxidase containig cells (eosinophils) peaked on day 7/4 p.i./p.t., whereas infection with BZ-susceptible strain elicited massive accumulation of these cells on day 4/1 p.i./p.t., particularly in the submucosa. No marked differences in eosinophils localisation were observed between both groups after the therapy. Goblet cells were found only in the proximal parts of glandulae gastricae close to the mucosal surface and no differences in the distribution in the stomach wall of both groups of animals were observed. After therapy the higher larval counts in case of BZ-resistant strain were in the correlation with the lower decline of CTMC and eosinophils, but MMC numbers were not significantly different between both treated groups. Present data indicate that in early stage post infection, the distribution of individual innate immunity cells might be directly affected by the larvae, and that the genetic and consequently biological differences related to the ... resistance to benzimidazoles probably had the impact on the interactions of larvae with the different immune cells in their niche.

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In vitro and in vivo characterization of p-amino-phenethyl-m-trifluoromethylphenyl piperazine (PAPP), a novel serotonergic agonist with anthelmintic activity against Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis

Cited by 19 publications

References 15 publications

A modified in vitro larvae migration inhibition assay using rumen fluid to evaluate Haemonchus contortus viability

A modified in vitro larvae migration inhibition assay using rumen fluid to evaluate Haemonchus contortus viability

Ion channels and receptor as targets for the control of parasitic nematodes

Effect of albendazole therapy on susceptible and resistant Haemonchus contortus larvae in Mongolian gerbils (Meriones unguiculatus) and distribution of inflammatory cells in the stomach wall

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