TY  - JOUR
AU  - Stojković, Maja
AU  - Todorović, Zoran
AU  - Protić, Dragana
AU  - Stevanović, Strahinja
AU  - Medić, Dragana
AU  - Charvet, Claude L.
AU  - Marjanović, Djordje
AU  - Nedeljković Trailović, Jelena
AU  - Trailović, Saša M.
PY  - 2024
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/3564
AB  - The control of parasitic nematode infections relies mostly on anthelmintics. The potential pharmacotherapeutic application of phytochemicals, in order to overcome parasite resistance and enhance the effect of existing drugs, is becoming increasingly important. The antinematodal effects of carveol was tested on the free-living nematode Caenorhabditis elegans and the neuromuscular preparation of the parasitic nematode Ascaris suum. Carveol caused spastic and geraniol atonic paralysis in C. elegans. In A. suum carveol potentiated contractions induced by acetylcholine (ACh) and this effect was confirmed with two-electrode voltage-clamp electrophysiology on the A. suum nicotinic acetylcholine receptor expressed in Xenopus oocytes. However, potentiating effect of carveol on ACh-induced contractions was partially sensitive to atropine, indicates a dominant nicotine effect but also the involvement of some muscarinic structures. The effects of carveol on the neuromuscular system of mammals are also specific. In micromolar concentrations, carveol acts as a non-competitive ACh antagonist on ileum contractions. Unlike atropine, it does not change the EC50 of ACh but reduces the amplitude of contractions. Carveol caused an increase in Electrical Field Stimulation-evoked contractions of the isolated rat diaphragm, but at higher concentrations it caused an inhibition. Also, carveol neutralized the mecamylamine-induced tetanic fade, indicating a possibly different pre-and post-synaptic action at the neuromuscular junction.
PB  - Frontiers Media
T2  - Frontiers in Pharmacology
T1  - Pharmacological effects of monoterpene carveol on the neuromuscular system of nematodes and mammals
VL  - 15
DO  - 10.3389/fphar.2024.1326779
ER  - 

@article{
author = "Stojković, Maja and Todorović, Zoran and Protić, Dragana and Stevanović, Strahinja and Medić, Dragana and Charvet, Claude L. and Marjanović, Djordje and Nedeljković Trailović, Jelena and Trailović, Saša M.",
year = "2024",
abstract = "The control of parasitic nematode infections relies mostly on anthelmintics. The potential pharmacotherapeutic application of phytochemicals, in order to overcome parasite resistance and enhance the effect of existing drugs, is becoming increasingly important. The antinematodal effects of carveol was tested on the free-living nematode Caenorhabditis elegans and the neuromuscular preparation of the parasitic nematode Ascaris suum. Carveol caused spastic and geraniol atonic paralysis in C. elegans. In A. suum carveol potentiated contractions induced by acetylcholine (ACh) and this effect was confirmed with two-electrode voltage-clamp electrophysiology on the A. suum nicotinic acetylcholine receptor expressed in Xenopus oocytes. However, potentiating effect of carveol on ACh-induced contractions was partially sensitive to atropine, indicates a dominant nicotine effect but also the involvement of some muscarinic structures. The effects of carveol on the neuromuscular system of mammals are also specific. In micromolar concentrations, carveol acts as a non-competitive ACh antagonist on ileum contractions. Unlike atropine, it does not change the EC50 of ACh but reduces the amplitude of contractions. Carveol caused an increase in Electrical Field Stimulation-evoked contractions of the isolated rat diaphragm, but at higher concentrations it caused an inhibition. Also, carveol neutralized the mecamylamine-induced tetanic fade, indicating a possibly different pre-and post-synaptic action at the neuromuscular junction.",
publisher = "Frontiers Media",
journal = "Frontiers in Pharmacology",
title = "Pharmacological effects of monoterpene carveol on the neuromuscular system of nematodes and mammals",
volume = "15",
doi = "10.3389/fphar.2024.1326779"
}

Stojković, M., Todorović, Z., Protić, D., Stevanović, S., Medić, D., Charvet, C. L., Marjanović, D., Nedeljković Trailović, J.,& Trailović, S. M.. (2024). Pharmacological effects of monoterpene carveol on the neuromuscular system of nematodes and mammals. in Frontiers in Pharmacology
Frontiers Media., 15.
https://doi.org/10.3389/fphar.2024.1326779

Stojković M, Todorović Z, Protić D, Stevanović S, Medić D, Charvet CL, Marjanović D, Nedeljković Trailović J, Trailović SM. Pharmacological effects of monoterpene carveol on the neuromuscular system of nematodes and mammals. in Frontiers in Pharmacology. 2024;15.
doi:10.3389/fphar.2024.1326779 .

Stojković, Maja, Todorović, Zoran, Protić, Dragana, Stevanović, Strahinja, Medić, Dragana, Charvet, Claude L., Marjanović, Djordje, Nedeljković Trailović, Jelena, Trailović, Saša M., "Pharmacological effects of monoterpene carveol on the neuromuscular system of nematodes and mammals" in Frontiers in Pharmacology, 15 (2024),
https://doi.org/10.3389/fphar.2024.1326779 . .

TY  - JOUR
AU  - Marjanović, Đorđe
AU  - Zdravković, Nemanja
AU  - Milovanović, Mirjana
AU  - Nedeljković-Trailović, Jelena
AU  - Robertson, Alan P.
AU  - Todorović, Zoran
AU  - Trailović, Saša
PY  - 2020
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/1807
AB  - The 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.
PB  - Elsevier, Amsterdam
T2  - Veterinary Parasitology
T1  - 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
VL  - 278
SP  - UNSP 109031
DO  - 10.1016/j.vetpar.2020.109031
ER  - 

@article{
author = "Marjanović, Đorđe and Zdravković, Nemanja and Milovanović, Mirjana and Nedeljković-Trailović, Jelena and Robertson, Alan P. and Todorović, Zoran and Trailović, Saša",
year = "2020",
abstract = "The 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.",
publisher = "Elsevier, Amsterdam",
journal = "Veterinary Parasitology",
title = "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",
volume = "278",
pages = "UNSP 109031",
doi = "10.1016/j.vetpar.2020.109031"
}

Marjanović, Đ., Zdravković, N., Milovanović, M., Nedeljković-Trailović, J., Robertson, A. P., Todorović, Z.,& Trailović, S.. (2020). 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. in Veterinary Parasitology
Elsevier, Amsterdam., 278, UNSP 109031.
https://doi.org/10.1016/j.vetpar.2020.109031

Marjanović Đ, Zdravković N, Milovanović M, Nedeljković-Trailović J, Robertson AP, 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. in Veterinary Parasitology. 2020;278:UNSP 109031.
doi:10.1016/j.vetpar.2020.109031 .

Marjanović, Đorđe, Zdravković, Nemanja, Milovanović, Mirjana, Nedeljković-Trailović, Jelena, Robertson, Alan P., Todorović, Zoran, Trailović, Saša, "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" in Veterinary Parasitology, 278 (2020):UNSP 109031,
https://doi.org/10.1016/j.vetpar.2020.109031 . .