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Monepantel is a non-competitive antagonist of nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum

Overview of attention for article published in International Journal of Parasitology: Drugs and Drug Resistance, December 2017
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Title
Monepantel is a non-competitive antagonist of nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum
Published in
International Journal of Parasitology: Drugs and Drug Resistance, December 2017
DOI 10.1016/j.ijpddr.2017.12.001
Pubmed ID
Authors

Melanie Abongwa, Djordje S. Marjanovic, James G. Tipton, Fudan Zheng, Richard J. Martin, Sasa M. Trailovic, Alan P. Robertson

Abstract

Zolvix® is a recently introduced anthelmintic drench containing monepantel as the active ingredient. Monepantel is a positive allosteric modulator of DEG-3/DES-2 type nicotinic acetylcholine receptors (nAChRs) in several nematode species. The drug has been reported to produce hypercontraction of Caenorhabditis elegans and Haemonchus contortus somatic muscle. We investigated the effects of monepantel on nAChRs from Ascaris suum and Oesophagostomum dentatum heterologously expressed in Xenopus laevis oocytes. Using two-electrode voltage-clamp electrophysiology, we studied the effects of monepantel on a nicotine preferring homomeric nAChR subtype from A. suum comprising of ACR-16; a pyrantel/tribendimidine preferring heteromeric subtype from O. dentatum comprising UNC-29, UNC-38 and UNC-63 subunits; and a levamisole preferring subtype (O. dentatum) comprising UNC-29, UNC-38, UNC-63 and ACR-8 subunits. For each subtype tested, monepantel applied in isolation produced no measurable currents thereby ruling out an agonist action. When monepantel was continuously applied, it reduced the amplitude of acetylcholine induced currents in a concentration-dependent manner. In all three subtypes, monepantel acted as a non-competitive antagonist on the expressed receptors. ACR-16 from A. suum was particularly sensitive to monepantel inhibition (IC50 values: 1.6 ± 3.1 nM and 0.2 ± 2.3 μM). We also investigated the effects of monepantel on muscle flaps isolated from adult A. suum. The drug did not significantly increase baseline tension when applied on its own. As with acetylcholine induced currents in the heterologously expressed receptors, contractions induced by acetylcholine were antagonized by monepantel. Further investigation revealed that the inhibition was a mixture of competitive and non-competitive antagonism. Our findings suggest that monepantel is active on multiple nAChR subtypes.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 16%
Lecturer 4 11%
Student > Ph. D. Student 4 11%
Researcher 4 11%
Professor 2 5%
Other 5 13%
Unknown 13 34%
Readers by discipline Count As %
Veterinary Science and Veterinary Medicine 5 13%
Biochemistry, Genetics and Molecular Biology 5 13%
Agricultural and Biological Sciences 4 11%
Nursing and Health Professions 2 5%
Medicine and Dentistry 2 5%
Other 5 13%
Unknown 15 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 January 2018.
All research outputs
#16,053,755
of 25,382,440 outputs
Outputs from International Journal of Parasitology: Drugs and Drug Resistance
#229
of 407 outputs
Outputs of similar age
#251,189
of 444,112 outputs
Outputs of similar age from International Journal of Parasitology: Drugs and Drug Resistance
#4
of 7 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 407 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one is in the 38th percentile – i.e., 38% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 444,112 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.