The effects of pyrantel tartrate on Sarcocystis neurona merozoite viability.

Sarcocystis neurona is the etiologic agent of equine protozoal myeloencephalitis, a neurologic disease of horses. The present study was designed to test the hypothesis that pyrantel tartrate can kill S. neurona merozoites growing in equine dermal cell culture. Sarcocystis neurona merozoites were exposed to a range of concentrations of pyrantel tartrate or sodium tartrate ranging from 0.001 to 0.01 M. Merozoites were then placed onto equine dermal cell cultures and incubated for 2 weeks to check for viability. At 1 and 2 weeks after inoculation, plaque counts were compared between treatments and, between treatments and controls. Merozoites exposed to concentrations of pyrantel tartrate higher than 0.0025 M (8.91 x 10(-4) g/ml) did not produce plaques in equine dermal cells, whereas those exposed to similar concentrations of the tartrate salt or medium alone produced significant numbers of plaques. These results demonstrate that pyrantel tartrate has activity against S. neurona merozoites in vitro and suggest that it may have activity against the sporozoite stage of the parasite found in the equine gut.

Experimental cyathostome challenge of ponies maintained with or without benefit of daily pyrantel tartrate feed additive: comparison of parasite burdens, immunity and colonic pathology.

Eighteen mixed-breed, naturally infected ponies ranging in age from 1 to 16 yr and four cyathostome-naïve ponies reared and maintained under parasite-free conditions ranging in age from 1 to 4 yr were used in this study. Naturally-infected ponies were treated with 1 dose of ivermectin (IVM) at 200 micrograms kg-1, followed by a 5-day regimen of oxibendazole (OBZ) at 20 mg kg-1 to remove existing cyathostome burdens; cyathostome-naïve control ponies were treated with IVM alone. The naturally infected ponies were matched on age and gender, then randomly assigned to one of three treatment groups of six animals per group; the four cyathostome-naïve ponies constituted a fourth group. Following OBZ treatment, Group 1 ponies were treated with pyrantel tartrate (PT) in their pelleted ration; the remaining ponies received only the pelleted ration. Beginning on experiment Day 3, a daily challenge infection of 10(4) mixed cyathostome larvae was administered orally to ponies of Group 1, Group 2 and the cyathostome-naïve controls. Group 3 ponies served as unchallenged controls to determine residual parasite burdens following IVM/OBZ treatment. Necropsy examinations were performed on three Group 3 ponies on Day 1; the remainder of the necropsy examinations began on Day 41. Cyathostome burdens were evaluated by recovery of larvae and adults from the luminal contents, by digestions of the intestinal mucosa, and by mural transillumination of full-thickness intestinal sections. Differences in postchallenge clinical responses were also compared. Necropsy examinations included comparisons of grossly visible inflammation of the large bowel, weights of biopsy specimens from each region, and histologic evaluations of these biopsies. Parasite recoveries at necropsy indicated a strong protective effect derived from daily PT treatment. Mean weights of intestinal biopsies corresponded with worm burdens, but histological evaluation did not reveal architectural or cellular changes to account for the increase in weight; therefore, edema was suspected. A strong age-related resistance to challenge infection was apparent in both the PT-treated and control groups by virtue of the lower mean worm burdens found in older ponies compared to younger ponies of the same treatment group; however, daily PT treatment of older ponies reduced the variability of their worm burdens to a uniformly low level. Comparisons of luminal and mucosal parasite burdens of age stratified nontreated controls further suggest that the age related resistance, which is acquired, targets increasing numbers of parasite stages as this resistance matures. Further, there is no evidence for an immune mediated acquisition of hypobiotic L3.

A microlarval development assay for the detection of anthelmintic resistance in sheep nematodes.

A microlarval development test for the detection of anthelmintic resistance in nematodes is described. Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis eggs were cultured to third stage larvae in the presence of Earle's balanced salt solution, yeast extract and bacteria in a total volume of 150 microliters. Good dose-response data were obtained with thiabendazole, levamisole, pyrantel tartrate and ivermectin allowing the determination of the 50 per cent lethal concentration and of resistance factors when resistant strains were available. The test was found to be accurate, sensitive, easy to carry out and applicable to the routine detection of resistance.

Effects of diethylcarbamazine on the motility of Angiostrongylus cantonensis and Dirofilaria immitis.

Effects of piperazine derivatives, especially of diethylcarbamazine (DEC) on adult Angiostrongylus cantonensis and Dirofilaria immitis were examined. Piperazine (3 X 10(-5)-10(-4) M) paralyzed A. cantonensis and the action was antagonized by picrotoxin. 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) (10(-5)-10(-4) M) caused contraction but little effect was produced by strychnine. An inhibitory effect on untreated preparations was caused by lower concentrations (3 X 10(-6)-10(-5) M) of diethylcarbamazine citrate (DEC) and also on the preparations contracted by eserine. A stimulatory effect was also seen when higher concentrations (10(-4)-3 X 10(-4) M) of this drug were applied to both preparations. The inhibitory action of DEC was antagonized by gabergic antagonists such as picrotoxin and bicuculline, but not by alpha-adrenergic antagonists like dibenamine and phentolamine. When the worm preparation was paralyzed by strychnine or hexylresorcinol (inhibitors of the release of acetylcholine in this worm), the stimulatory effect of DEC was blocked, but pyrantel (a nicotinic cholinergic agonist) contracted the paralyzed preparation. However, the effect of DEC on D. immitis (10(-7)-3 X 10(-4) M) was inhibitory, and this action was also antagonized by picrotoxin. These results suggest that the DEC inhibitory and stimulatory action is through the gabergic and cholinergic mechanisms in adult A. cantonensis and D. immitis.

Studies on chemotherapy of parasitic helminths (XVIII). Mechanism of spastically paralyzing action of pyrantel in Angiostrongylus cantonensis.

Pyrantel tartrate caused spastic paralysis through stimulating nicotinic cholinoceptors in Angiostrongylus cantonensis.

Studies on chemotherapy of parasitic helminths (XVII). Effects of pyrantel on the motility of various parasitic helminths and isolated host tissues.

Pyrantel tartrate caused spastic paralysis in various parasitic nematodes, but not in cestodes and trematodes.

Drug interactions of levamisole with pyrantel tartrate and dichlorvos in pigs.

The LD50 from subcutaneous administration of levamisole in castrated male pigs (15 to 25 kg) was established as 39.8 mg/kg. Oral administration of dichlorvos (60 mg/kg, 3 times the anthelmintic dosage level) 1 hour before levamisole injection lowered blood cholinesterase activity to approximately 60% that of the controls, but did not change the LD50 of levamisole. In contrast, oral administration of pyrantel tartrate (25 mg/kg, an anthelmintic dosage level) did not lower blood cholinesterase activity, but rather, increased the toxicity by lowering the LD50 of levamisole from 39.8 mg/kg to 27.5 mg/kg. The data supported the hypothesis that levamisole toxicity was enhanced by nicotine-like compounds (ie, pyrantel), but was not affected by organophosphates (ie, dichlorvos).