Carvacrol acts as a potent selective antagonist of different types of nicotinic acetylcholine receptors and potentiates the effect of monepantel in the parasitic nematode Ascaris suum

Publication date: Available online 20 January 2020Source: Veterinary ParasitologyAuthor(s): Djordje S. Marjanović, Nemanja Zdravković, Mirjana Milovanović, Jelena Nedeljković Trailović, Alan P. Robertson, Zoran Todorović, Saša M. TrailovićAbstractThe 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 100μM decreased the Emax of pyrantel, morantel and bephenium by 29%, 39% and 12% respectively. The EC50 ratio was 3.43, 2.95 and 2.47 for pyrantel, morantel and bephinium, respectively. Carvacrol 300 u M reduces the Emax of pyrantel, morantel and bephenium by 71%, 80% and 75% respectively. The EC50 ratio for pyrantel, morantel and bephenium was 3.88, 3.19 and 4.83 respectively. Furthermore, carvacrol signifi...
Source: Veterinary Parasitology - Category: Veterinary Research Source Type: research