Derquantel and abamectin: Effects and interactions on isolated tissues of Ascaris suum
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2013
Authors
Puttachary, S.Trailović, Saša
Robertson, Alan P.
Thompson, D.P.
Woods, D.J.
Martin, Richard J.
Article (Published version)
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Startect® is a novel anthelmintic combination of derquantel and abamectin. It is hypothesized that derquantel and abamectin interact pharmacologically. We investigated the effects of derquantel, abamectin and their combination on somatic muscle nicotinic acetylcholine receptors and pharyngeal muscle glutamate gated chloride receptor channels of Ascaris suum. We used muscle-strips to test the effects of abamectin, derquantel, and abamectin + derquantel together on the contraction responses to different concentrations of acetylcholine. We found that abamectin reduced the response to acetylcholine, as did derquantel. In combination (abamectin + derquantel), inhibition of the higher acetylcholine concentration response was greater than the predicted additive effect. A two-micropipette current-clamp technique was used to study electrophysiological effects of the anthelmintics on: (1) acetylcholine responses in somatic muscle and; (2) on l-glutamate responses in pharyngeal preparations. On s...omatic muscle, derquantel (0.1-30 μM) produced a potent (IC50 0.22, CI 0.18-0.28 μM) reversible antagonism of acetylcholine depolarizations. Abamectin (0.3 μM) produced a slow onset inhibition of acetylcholine depolarizations. We compared effects of abamectin and derquantel on muscle preparations pretreated for 30 min with these drugs. The effect of the combination was significantly greater than the predicted additive effect of both drugs at higher acetylcholine concentrations. On the pharynx, application of derquantel produced no significant effect by itself or on responses to abamectin and l-glutamate. Abamectin increased the input conductance of the pharynx (EC50 0.42, CI 0.13-1.36 μM). Our study demonstrates that abamectin and derquantel interact at nicotinic acetylcholine receptors on the somatic muscle and suggested synergism can occur.
Keywords:
Abamectin / Combination / Derquantel / GluCls / Interaction / nAChRsSource:
Molecular and Biochemical Parasitology, 2013, 188, 2, 79-86Funding / projects:
- NIH NIAID R56 AI047194-11 to R.J.M., NIH NIAID 1R21AI092185-01A1 to APR and funding from Zoetis Animal Health to R.J.M. and A.P.R.
DOI: 10.1016/j.molbiopara.2013.02.004
ISSN: 0166-6851
PubMed: 23523993
WoS: 000320207300001
Scopus: 2-s2.0-84877083823
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Fakultet veterinarske medicineTY - JOUR AU - Puttachary, S. AU - Trailović, Saša AU - Robertson, Alan P. AU - Thompson, D.P. AU - Woods, D.J. AU - Martin, Richard J. PY - 2013 UR - https://vet-erinar.vet.bg.ac.rs/handle/123456789/1068 AB - Startect® is a novel anthelmintic combination of derquantel and abamectin. It is hypothesized that derquantel and abamectin interact pharmacologically. We investigated the effects of derquantel, abamectin and their combination on somatic muscle nicotinic acetylcholine receptors and pharyngeal muscle glutamate gated chloride receptor channels of Ascaris suum. We used muscle-strips to test the effects of abamectin, derquantel, and abamectin + derquantel together on the contraction responses to different concentrations of acetylcholine. We found that abamectin reduced the response to acetylcholine, as did derquantel. In combination (abamectin + derquantel), inhibition of the higher acetylcholine concentration response was greater than the predicted additive effect. A two-micropipette current-clamp technique was used to study electrophysiological effects of the anthelmintics on: (1) acetylcholine responses in somatic muscle and; (2) on l-glutamate responses in pharyngeal preparations. On somatic muscle, derquantel (0.1-30 μM) produced a potent (IC50 0.22, CI 0.18-0.28 μM) reversible antagonism of acetylcholine depolarizations. Abamectin (0.3 μM) produced a slow onset inhibition of acetylcholine depolarizations. We compared effects of abamectin and derquantel on muscle preparations pretreated for 30 min with these drugs. The effect of the combination was significantly greater than the predicted additive effect of both drugs at higher acetylcholine concentrations. On the pharynx, application of derquantel produced no significant effect by itself or on responses to abamectin and l-glutamate. Abamectin increased the input conductance of the pharynx (EC50 0.42, CI 0.13-1.36 μM). Our study demonstrates that abamectin and derquantel interact at nicotinic acetylcholine receptors on the somatic muscle and suggested synergism can occur. T2 - Molecular and Biochemical Parasitology T1 - Derquantel and abamectin: Effects and interactions on isolated tissues of Ascaris suum VL - 188 IS - 2 SP - 79 EP - 86 DO - 10.1016/j.molbiopara.2013.02.004 ER -
@article{ author = "Puttachary, S. and Trailović, Saša and Robertson, Alan P. and Thompson, D.P. and Woods, D.J. and Martin, Richard J.", year = "2013", abstract = "Startect® is a novel anthelmintic combination of derquantel and abamectin. It is hypothesized that derquantel and abamectin interact pharmacologically. We investigated the effects of derquantel, abamectin and their combination on somatic muscle nicotinic acetylcholine receptors and pharyngeal muscle glutamate gated chloride receptor channels of Ascaris suum. We used muscle-strips to test the effects of abamectin, derquantel, and abamectin + derquantel together on the contraction responses to different concentrations of acetylcholine. We found that abamectin reduced the response to acetylcholine, as did derquantel. In combination (abamectin + derquantel), inhibition of the higher acetylcholine concentration response was greater than the predicted additive effect. A two-micropipette current-clamp technique was used to study electrophysiological effects of the anthelmintics on: (1) acetylcholine responses in somatic muscle and; (2) on l-glutamate responses in pharyngeal preparations. On somatic muscle, derquantel (0.1-30 μM) produced a potent (IC50 0.22, CI 0.18-0.28 μM) reversible antagonism of acetylcholine depolarizations. Abamectin (0.3 μM) produced a slow onset inhibition of acetylcholine depolarizations. We compared effects of abamectin and derquantel on muscle preparations pretreated for 30 min with these drugs. The effect of the combination was significantly greater than the predicted additive effect of both drugs at higher acetylcholine concentrations. On the pharynx, application of derquantel produced no significant effect by itself or on responses to abamectin and l-glutamate. Abamectin increased the input conductance of the pharynx (EC50 0.42, CI 0.13-1.36 μM). Our study demonstrates that abamectin and derquantel interact at nicotinic acetylcholine receptors on the somatic muscle and suggested synergism can occur.", journal = "Molecular and Biochemical Parasitology", title = "Derquantel and abamectin: Effects and interactions on isolated tissues of Ascaris suum", volume = "188", number = "2", pages = "79-86", doi = "10.1016/j.molbiopara.2013.02.004" }
Puttachary, S., Trailović, S., Robertson, A. P., Thompson, D.P., Woods, D.J.,& Martin, R. J.. (2013). Derquantel and abamectin: Effects and interactions on isolated tissues of Ascaris suum. in Molecular and Biochemical Parasitology, 188(2), 79-86. https://doi.org/10.1016/j.molbiopara.2013.02.004
Puttachary S, Trailović S, Robertson AP, Thompson D, Woods D, Martin RJ. Derquantel and abamectin: Effects and interactions on isolated tissues of Ascaris suum. in Molecular and Biochemical Parasitology. 2013;188(2):79-86. doi:10.1016/j.molbiopara.2013.02.004 .
Puttachary, S., Trailović, Saša, Robertson, Alan P., Thompson, D.P., Woods, D.J., Martin, Richard J., "Derquantel and abamectin: Effects and interactions on isolated tissues of Ascaris suum" in Molecular and Biochemical Parasitology, 188, no. 2 (2013):79-86, https://doi.org/10.1016/j.molbiopara.2013.02.004 . .