Pyrantel

Abstract: Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole), tetrahydropyrimidines (pyrantel) and macrocyclic lactones (ivermectin, moxidectin). Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantially reduced clinical disease, especially that associated with large strongyle species; however, high treatment frequency has led to considerable selection pressure for anthelmintic resistance, particularly in cyathostomin species. Field studies published over the last decade indicate that benzimidazole resistance is widespread globally in cyathostomins and there are also many reports of resistance to pyrantel in these worms. Cyathostomin resistance to macrocyclic lactone compounds is emerging, principally measured as a reduction in strongyle egg reappearance time observed after treatment. Ivermectin resistance is a further concern in the small intestinal nematode, Parascaris equorum, an important pathogen of foals. These issues indicate that horse nematodes must now be controlled using methods less dependent on anthelmintic use and more reliant on management practices designed to reduce the force of infection in the environment. Such strategies include improved grazing management integrated with targeted anthelmintic administration involving faecal egg count (FEC)-directed treatments. The latter require that the supporting diagnostic tests available are robust and practically applicable. Recent research has focused on maximising the value of FEC analysis in horses and on optimizing protocols for anthelmintic efficacy testing. Other studies have sought to develop diagnostics that will help define levels of pre-patent infection. This review describes recent advances in each of these areas of research.

Abstract: Intracellular current and voltage clamp techniques were used to investigate the mode of action of the anthelmintics, morantel, pyrantel and levamisole applied to the bag region of Ascaris suum muscle cells. Microperfusion of the anthelmintics and of O-acetylcholine (ACh) increased the input conductance and depolarised the membrane potential of the muscle bags. The relative potencies of these drugs were determined from dose–conductance relationships and found to be: morantel = pyrantel > levamisole > ACh. High doses (>10μM) of morantel caused antagonism of ACh responses. ACh-induced currents were measured under voltage clamp (over the range −80 to +10mV). At membrane potentials between −80 and 0 mV, microperfusion of ACh induced a voltage-dependent inward current. The current–voltage relationship was linear for membrane potentials in the range −30 to +10mV. The reversal potential was measured directly and found to be about +10mV. The relationship became non-linear at membrane potentials more negative than −30 mV, and the degree of non-linearity was dependent upon the concentration of ACh. The current–voltage relationships for morantel, pyrantel and levamisole also possessed both linear (−30 to 0mV) and non-linear components. The reversal potential for each agonist, determined by extrapolation of the linear component of the current–voltage relationship, was approximately +10mV, indicating the same cation channels were activated both by ACh and the anthelmintics. Evidence for competition between ACh and pyrantel for the same membrane receptor was obtained using iontophoretic delivery of each agonist from a double-barrelled micropipette. It is concluded that the anthelmintics, morantel, pyrantel and levamisole act as potent agonists at ACh receptors on muscle bag membranes of A. suum.

Abstract: Caenorhabditis elegans maintained on ampicillin-treated Escherichia coli has been found to be sensitive to the benzimidazole anthelmintics, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, thiabendazole and the non-benzimidazoles, avermectin B1a, bitoscanate, febantel, levamisole, morantel, nitroscanate, oxantel, phenothiazine, pyrantel, pyrvinium pamoate, rafoxanide and stilbazium iodide at concentrations of 50 μg cm−3 or less. It can therefore be used in a high through-put in vitro pre-screen for anthelmintics. It is suggested that C. elegans may also be useful for evaluating the mode of action of drugs and the mechanism of resistance of nematodes to anthelmintics.