Neuromuscular System of Nematodes Is a Target of Synergistic Pharmacological Effects of Carvacrol and Geraniol

<b>Background:</b> The active ingredients of essential plant oils appear as potentially effective antinematodal drugs or substances that can potentiate the action of already-existing anthelmintics. So far, we have verified that, aside from the direct effect on the neuromuscular system of nematodes, some of them can potentiate the effects of drugs that are agonists or antagonists of nematode cholinergic receptors. <b>Methods:</b> In this study, the antinematodal effects of geraniol and carvacrol were compared, as well as their interaction in the experimental model <i>Caenorhabditis elegans</i>, on the contractile properties of <i>Ascaris suum</i> neuromuscular preparations and on the ACR-16 nicotinic acetylcholine receptor (nAChR) of <i>A. suum</i> expressed in Xenopus leavis oocytes. <b>Results:</b> The combination of geraniol and carvacrol showed a synergistic nematocidal effect in the tests on <i>C. elegans</i>, reducing the value of individual LC₅₀ by almost 10-times. This combination also exerted a synergistic inhibitory effect on the contractions of <i>A. suum</i>, significantly increased the EC₅₀ of ACh and reduced the maximal contractile effect. The synergistic interaction of these two monoterpenes on Asu-ACR-16 nAChR expressed in Xenopus oocytes resulted in a significant decrease in the maximum current, while the ACh EC₅₀ value remained unchanged. <b>Conclusions:</b> Our findings provide a better understanding of the mode of action of monoterpene plant compounds. The possible antiparasitic application of active ingredients of essential plant oils that exhibit a synergistic anthelmintic effect represents an important basis for the development of new drugs and new therapeutic procedures.