Oxantel is an N-type (methyridine and nicotine) agonist not an L-type (levamisole and pyrantel) agonist: classification of cholinergic anthelmintics in Ascaris
Abstract
Three pharmacological subtypes of cholinergic receptors have been distinguished in Ascaris suum using a muscle contraction assay and
classical pharmacological techniques. The receptor subtypes are: a B-subtype (sensitive to bephenium); an L-subtype (sensitive to levamisole
and pyrantel); and an N-subtype (sensitive to nicotine and methyridine). Oxantel is a cholinergic anthelmintic that was first introduced for the
treatment of whipworm, Trichuris, infections in children. Here, we compare the subtype selectivity of oxantel with thenium and other
cholinergic anthelmintics. We used the A. suum assay to derive pA2 values for the agonists: oxantel, thenium, bephenium, levamisole,
pyrantel, nicotine and methyridine with the antagonists: paraherquamide, 2-desoxyparaherquamide and methyllycaconitine. pA2 values,
rather than pKB values, were determined for all agonists when it was found that Schild slopes for some agonists were significantly less than
1.0. The pA2 of oxantel was 6.58 ^ ...0.25 for paraherquamide; 5.39 ^ 0.28 for 2-desoxyparaherquamide; 7.01 ^ 0.19 for methyllycaconitine.
Comparison of pA2 values using cluster analysis showed that oxantel was grouped with nicotine and methyridine, the N-subtype agonists.
Thenium had pA2s of 7.84 ^ 0.41 for paraherquamide; 5.52 ^ 0.50 for 2-desoxyparaherquamide; 6.33 ^ 0.19 for methyllycaconitine.
Cluster analysis placed thenium between the L-subtype agonists and the B-subtype agonist. The therapeutic significance of classification of
cholinergic anthelmintics is discussed. Combination of oxantel and pyrantel would have therapeutic advantages, covering N- and L-subtypes,
and so increasing spectrum of action and reducing the potential for development of resistance. Our results predict that oxantel may remain
effective in some nematode isolates that have become levamisole- and pyrantel-resistant.
Keywords:
Oxantel; Thenium; Bephenium; Levamisole; Pyrantel; Nicotine; ACh receptor; Receptor subtypesSource:
International journal for parasitology, 2004, 34, 1083-1090Publisher:
- Elsevier
Funding / projects:
- NIH R01 A14794 to Richard J. Martin.
Institution/Community
Fakultet veterinarske medicineTY - JOUR AU - Martin J., Richard AU - Clark L., Cheryl AU - Trailović, Saša M. AU - Robertson P., Alan PY - 2004 UR - https://vet-erinar.vet.bg.ac.rs/handle/123456789/2625 AB - Three pharmacological subtypes of cholinergic receptors have been distinguished in Ascaris suum using a muscle contraction assay and classical pharmacological techniques. The receptor subtypes are: a B-subtype (sensitive to bephenium); an L-subtype (sensitive to levamisole and pyrantel); and an N-subtype (sensitive to nicotine and methyridine). Oxantel is a cholinergic anthelmintic that was first introduced for the treatment of whipworm, Trichuris, infections in children. Here, we compare the subtype selectivity of oxantel with thenium and other cholinergic anthelmintics. We used the A. suum assay to derive pA2 values for the agonists: oxantel, thenium, bephenium, levamisole, pyrantel, nicotine and methyridine with the antagonists: paraherquamide, 2-desoxyparaherquamide and methyllycaconitine. pA2 values, rather than pKB values, were determined for all agonists when it was found that Schild slopes for some agonists were significantly less than 1.0. The pA2 of oxantel was 6.58 ^ 0.25 for paraherquamide; 5.39 ^ 0.28 for 2-desoxyparaherquamide; 7.01 ^ 0.19 for methyllycaconitine. Comparison of pA2 values using cluster analysis showed that oxantel was grouped with nicotine and methyridine, the N-subtype agonists. Thenium had pA2s of 7.84 ^ 0.41 for paraherquamide; 5.52 ^ 0.50 for 2-desoxyparaherquamide; 6.33 ^ 0.19 for methyllycaconitine. Cluster analysis placed thenium between the L-subtype agonists and the B-subtype agonist. The therapeutic significance of classification of cholinergic anthelmintics is discussed. Combination of oxantel and pyrantel would have therapeutic advantages, covering N- and L-subtypes, and so increasing spectrum of action and reducing the potential for development of resistance. Our results predict that oxantel may remain effective in some nematode isolates that have become levamisole- and pyrantel-resistant. PB - Elsevier T2 - International journal for parasitology T1 - Oxantel is an N-type (methyridine and nicotine) agonist not an L-type (levamisole and pyrantel) agonist: classification of cholinergic anthelmintics in Ascaris VL - 34 SP - 1083 EP - 1090 DO - 10.1016/j.ijpara.2004.04.014 ER -
@article{ author = "Martin J., Richard and Clark L., Cheryl and Trailović, Saša M. and Robertson P., Alan", year = "2004", abstract = "Three pharmacological subtypes of cholinergic receptors have been distinguished in Ascaris suum using a muscle contraction assay and classical pharmacological techniques. The receptor subtypes are: a B-subtype (sensitive to bephenium); an L-subtype (sensitive to levamisole and pyrantel); and an N-subtype (sensitive to nicotine and methyridine). Oxantel is a cholinergic anthelmintic that was first introduced for the treatment of whipworm, Trichuris, infections in children. Here, we compare the subtype selectivity of oxantel with thenium and other cholinergic anthelmintics. We used the A. suum assay to derive pA2 values for the agonists: oxantel, thenium, bephenium, levamisole, pyrantel, nicotine and methyridine with the antagonists: paraherquamide, 2-desoxyparaherquamide and methyllycaconitine. pA2 values, rather than pKB values, were determined for all agonists when it was found that Schild slopes for some agonists were significantly less than 1.0. The pA2 of oxantel was 6.58 ^ 0.25 for paraherquamide; 5.39 ^ 0.28 for 2-desoxyparaherquamide; 7.01 ^ 0.19 for methyllycaconitine. Comparison of pA2 values using cluster analysis showed that oxantel was grouped with nicotine and methyridine, the N-subtype agonists. Thenium had pA2s of 7.84 ^ 0.41 for paraherquamide; 5.52 ^ 0.50 for 2-desoxyparaherquamide; 6.33 ^ 0.19 for methyllycaconitine. Cluster analysis placed thenium between the L-subtype agonists and the B-subtype agonist. The therapeutic significance of classification of cholinergic anthelmintics is discussed. Combination of oxantel and pyrantel would have therapeutic advantages, covering N- and L-subtypes, and so increasing spectrum of action and reducing the potential for development of resistance. Our results predict that oxantel may remain effective in some nematode isolates that have become levamisole- and pyrantel-resistant.", publisher = "Elsevier", journal = "International journal for parasitology", title = "Oxantel is an N-type (methyridine and nicotine) agonist not an L-type (levamisole and pyrantel) agonist: classification of cholinergic anthelmintics in Ascaris", volume = "34", pages = "1083-1090", doi = "10.1016/j.ijpara.2004.04.014" }
Martin J., R., Clark L., C., Trailović, S. M.,& Robertson P., A.. (2004). Oxantel is an N-type (methyridine and nicotine) agonist not an L-type (levamisole and pyrantel) agonist: classification of cholinergic anthelmintics in Ascaris. in International journal for parasitology Elsevier., 34, 1083-1090. https://doi.org/10.1016/j.ijpara.2004.04.014
Martin J. R, Clark L. C, Trailović SM, Robertson P. A. Oxantel is an N-type (methyridine and nicotine) agonist not an L-type (levamisole and pyrantel) agonist: classification of cholinergic anthelmintics in Ascaris. in International journal for parasitology. 2004;34:1083-1090. doi:10.1016/j.ijpara.2004.04.014 .
Martin J., Richard, Clark L., Cheryl, Trailović, Saša M., Robertson P., Alan, "Oxantel is an N-type (methyridine and nicotine) agonist not an L-type (levamisole and pyrantel) agonist: classification of cholinergic anthelmintics in Ascaris" in International journal for parasitology, 34 (2004):1083-1090, https://doi.org/10.1016/j.ijpara.2004.04.014 . .