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dc.creatorMarjanović, Đorđe
dc.creatorZdravković, Nemanja
dc.creatorMilovanović, Mirjana
dc.creatorNedeljković-Trailović, Jelena
dc.creatorRobertson, Alan P.
dc.creatorTodorović, Zoran
dc.creatorTrailović, Saša
dc.date.accessioned2020-06-18T15:00:56Z
dc.date.available2021-01-16
dc.date.issued2020
dc.identifier.issn0304-4017
dc.identifier.urihttp://vet-erinar.vet.bg.ac.rs/handle/123456789/1841
dc.description.abstractThe neuromuscular system of parasitic nematodes has proven to be an efficient pharmacological target for antihelmintics. Some of the most frequently used antiparasitic drugs are agonists or antagonists of nicotinic acetylcholine receptors (nAChRs). The antinematodal mechanism of action of carvacrol involves the inhibition of parasite muscle contraction. We have examined the interaction of carvacrol with antinematodal drugs that are agonists of different subtypes of nAChRs and monepantel, which is a non-competitive antagonist of this receptor in A. suum. Additionally, we investigated the effect of carvacrol on the muscle type of nAChRs in the mammalian host. As orthosteric agonists of nAChR, pyrantel, morantel and befinijum lead to dose-dependent contractions of the neuromuscular preparation of Ascaris suum. Carvacrol 100 mu M decreased the E-max of pyrantel, morantel and bephenium by 29%, 39% and 12 %, 39 % and 12 % respectively. The EC50 ratio was 3.43, 2.95 and 2.47 for pyrantel, morantel and bephinium, respectively. Carvacrol 300 u mu M reduces the E-max of pyrantel, morantel and bephenium by 71%, 80% and 75 %, 80 % and 75 % respectively. The EC50 ratio for pyrantel, morantel and bephenium was 3.88, 3.19 and 4.83 respectively. Furthermore, carvacrol enhances the inhibitory effect of monepantel on A. mum contractions, which may have an effective clinical application. On the other hand, tested concentrations of carvacrol did not significantly affect the EFS-induced contractions of the rat diaphragm, indicating a lack of interaction with the postsynaptic nAChR at the muscle end plate in mammals, but the highest concentration (300 mu M) caused a clear tetanic fade. Carvacrol exhibited a time and dose-dependent effect on the Rota-rod performances of rats with a high value of the ED50 (421.6 mg/kg). In our research, carvacrol dominantly exhibited characteristics of a non-competitive antagonist of nAChR in A. suum, and enhances the inhibitory effect of monepantel. The combination of monepantel and carvacrol may be clinically very effective, and the carvacrol molecule itself can be used as a promising platform for the development of new anthelmintic drugs.en
dc.publisherElsevier, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Technological Development (TD or TR)/31087/RS//
dc.rightsembargoedAccess
dc.sourceVeterinary Parasitology
dc.subjectCarvacrolen
dc.subjectMonepantelen
dc.subjectA. suumen
dc.subjectnAChRen
dc.titleCarvacrol acts as a potent selective antagonist of different types of nicotinic acetylcholine receptors and enhances the effect of monepantel in the parasitic nematode Ascaris suumen
dc.typearticle
dc.rights.licenseBY-NC-ND
dcterms.abstractМарјановић, Ђорђе; Здравковић, Немања; Миловановић, Мирјана; Недељковић-Траиловић, Јелена; Робертсон, Aлан П.; Тодоровић, Зоран; Траиловић, Саша;
dc.citation.volume278
dc.citation.spageUNSP 109031
dc.citation.other278: UNSP 109031
dc.citation.rankM21~
dc.description.otherThis is the peer-reviewed version of the article: Marjanović, Đ.; Zdravković, N.; Milovanović, M.; Nedeljković-Trailović, J.; Robertson, A. P.; Todorović, Z.; Trailović, S. Carvacrol Acts as a Potent Selective Antagonist of Different Types of Nicotinic Acetylcholine Receptors and Enhances the Effect of Monepantel in the Parasitic Nematode Ascaris Suum. Veterinary Parasitology 2020, 278, UNSP 109031. [https://doi.org/10.1016/j.vetpar.2020.109031]
dc.identifier.wos000517852700012
dc.identifier.doi10.1016/j.vetpar.2020.109031
dc.identifier.pmid32032866
dc.identifier.scopus2-s2.0-85078737583
dc.type.versionacceptedVersion


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