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An investigational drug (2-picoline, 6-amino-4-nitro-, 1-oxide) was evaluated to characterize the anti-coccidial spectrum of the compound. Two concentrations of the drug (125 and 250 ppm) were evaluated for bioactivity; weight gain, survival, dropping, and lesion scores were the response variables utilized to ascertain activity. The activities of the picoline derivative were compared with monensin, maduramicin, and a narasin/nicarbazin (1:1) combination. The investigational drug had significant activity against Eimeria tenella and Eimeria necatrix, and the 250-ppm level was significantly more active than 125 ppm. At 250 ppm, the E. tenella activity of the picoline derivative was comparable to both monensin (120 ppm) and the 50-ppm narasin/nicarbazin combination, significantly less effective than maduramicin (6 ppm), and significantly more efficacious than 30 ppm narasin/nicarbazin. At the same level (250 ppm), the picoline derivative had significantly less E. necatrix activity than monensin (120 ppm), maduramicin (6 ppm), and narasin/nicarbazin (50 ppm), and significantly greater activity than 30 ppm narasin/nicarbazin. At best, only extremely weak Eimeria acervulina, Eimeria brunetti, and Eimeria maxima activities were noted with the investigational drug; higher concentrations of the picoline derivative may achieve greater anti-coccidial activity against these species. The efficacy of narasin/nicarbazin compared favorably with monensin and maduramicin; the 50-ppm level of the combination appeared significantly more efficacious than 30-ppm.

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Electrochemical data were acquired for several categories of anthelmintic agents, namely, iminium-type ions, metal derivatives and chelators, quinones and iminoquinones, and nitroheterocycles. Reductions usually were in the favorable range of +0.2 to -0.7 V versus normal hydrogen electrode. The drug effect is believed to result in part from either the catalytic production of oxidative stress or disruption of helminth electron transport systems. Relevant literature results are discussed.

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PGE1 and PGE2 have been reported to enhance natural expulsion of Nippostrongylus brasiliensis, a nematode parasite, from the intestine of the rat. Mucus production may also be a key element of worm rejection. Our study attempts to determine if 1) PGE1 or PGE2 alter the normal course of infection with N. brasiliensis in rats, 2) a known mucous enhancing drug, acetazolamide, can augment the rate of worm expulsion, and 3) combinations of prostaglandins and acetazolamide affect N. brasiliensis in the rat. Rats were inoculated with approximately 1,000 infective larvae of N. brasiliensis. Animals were administered, intraduodenally, one of the following: 0.2 ml 0.9% NaCl; 0.2 ml 100% ethanol; 250 micrograms PGE1/0.2 ml 100% ethanol; 250 micrograms PGE2/0.2 ml 100% ethanol; 250 micrograms acetazolamide/0.2 ml 100% ethanol; 250 micrograms PGE1 or PGE2 + 250 micrograms acetazolamide/0.2 ml 100% ethanol. These solutions were given in a single bolus on day 6 postinoculation (PI) or twice daily on days 6-9 PI. Following these treatments the number of parasite ova per gram feces per day for days 6-10 PI and numbers of worms present at necropsy on day 10 PI were determined. Treatment with prostaglandins or acetazolamide or both failed to adversely affect egg deposition by adult female worms or the number of worms in the small intestine. These results do not support the involvement of prostaglandins in the expulsion of N. brasiliensis from the host intestine.

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Alborixin, a polyether antibiotic with ionophore properties, was evaluated to determine the effect of the drug on weight gain of chickens and to define the anticoccidial spectrum of activity. The 50-ppm concentration in the diet was identified as the maximum level that did not significantly reduce weight gain beyond that of monensin (standard drug); consequently, the drug was evaluated for anticoccidial activity at this dilution. At the 50-ppm level, alborixin demonstrated broad-spectrum anticoccidial activity; however, the drug lacked Eimeria necatrix efficacy. Monensin and maduramycin were significantly more efficacious than alborixin as a treatment for several species of Eimeria. Higher concentrations of alborixin (greater than 50 ppm) appear essential to achieve broad-spectrum and comparable anticoccidial activity, however, these levels substantially depressed weight gains. Alborixin is similar to many other polyethers in that weight gains are adversely affected at drug levels essential for solid broad-spectrum anticoccidial activity.

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Floor-pen studies were conducted to ascertain whether coccidiosis could be prevented by using a drug added to the litter to preclude coprophagia and ingestion of infective oocysts. An experimental drug (1-pyrrolidinebutyramide, 2-methyl-alpha,alpha-diphenyl) was added to litter contaminated with sporulated Eimeria tenella oocysts. Thereafter 7-day-old broiler chicks were reared on the litter for a nine-day period. Mortality, lesion scores and dropping scores were the criteria selected to determine efficacy. Treatment of the litter at the lowest level (2.3 g kg-1) did not reduce the incidence or severity of the disease, whereas treatment at two higher levels (11.5 and 23.0 g kg-1) significantly reduced both (incidence and severity). The highest level was the most efficacious; however, drug toxicity was also encountered at this level.

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A topical formulation of amitraz (Mitaban Liquid Concentrate, The Upjohn Company, Kalamazoo, Michigan, U.S.A.) was evaluated as a tick repellent and detachment agent, and flea repellent. The diluted liquid concentrate (250 p.p.m. active drug) was topically applied as a single treatment to dogs; the concentration was identical to the rate recommended for treatment of demodicosis and scabies. Brown dog tick (Rhipicephalus sanguineus) and American dog tick (Dermacentor variabilis) populations were eliminated and repelled. Repellent activity (92-95%) was observed against R. sanguineus for 2 weeks post-treatment; the treatment was moderately active (63%) during the third week, and at 4 weeks post-treatment the drug was inactive. Established R. sanguineus populations were also treated, and the diluted liquid concentrate had 100% tick-detachment efficacy. Repellent activity (99%) was also detected against D. variabilis; the activity was monitored for only 7 days. The ectoparasiticide had low to moderate flea (Ctenocephalides felis) repellent activity (42%) for 4 days post-treatment; thereafter the treatment was ineffective. Side-effects were not observed in any of the dogs treated with amitraz, or the placebo.

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Thirty dogs (20 treated, 10 controls) with naturally-acquired generalized demodicosis were utilized to evaluate the bio-activity and safety of a liquid concentrate formulation of amitraz, with or without the addition of a nonionic detergent. The detergent was added to the treatment mixture to enhance wetting and thereby reduce the number of treatments required to return diseased animals to a normal state. Three--six miticide treatments were topically applied to dogs at 14-day intervals, at a concentration of 250 parts per million active drug. The liquid concentrate with or without detergent, was equally effective and safe as a dermatotherapy for demodicosis; addition of the nonionic detergent grossly improved the wetting characteristics of the treatment mixture; however, it did not alter the biological activity or the safety of the therapy.

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A liquid concentrate formulation of amitraz was clinically evaluated in 1721 canines showing demodicosis, by 25 veterinary investigators. The therapy was applied topically at 14-day intervals, and at a concentration of 250 ppm active drug in water. The miticide was efficacious and safe; approximately 99% of the canines showing localized or generalized demodicosis became clinically normal, and the side-effects recorded were minimal and transient. Approximately 3/4 of the patients were pure-bred animals and the majority were less than 1 year old. The clinical data support the conclusion that amitraz (liquid concentrate) is efficacious and safe for treating canine demodicosis.

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A liquid concentrate formulation of amitraz (Mitaban: Upjohn) was used to topically treat 181 dogs with scabies, at an active drug level of 250 ppm, or 10.6 ml of concentrate in 2 gal water. After the dogs were clipped and bathed, the diluted medication was applied and allowed to dry on the animal. All treated dogs were clinically improved and 97.8% cured after a single treatment; 3 dogs required 2 treatments and 1 dog 3 treatments. Otodectes cynotis and Cheyletiella yasguri in several dogs were also cleared after 1 treatment. Mild, transient sedation occurred in 12.4% of treated dogs, with transient vomiting, increased appetite and diarrhea in less than 1%.

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Forty dogs (20 treated, 20 controls) were utilized to evaluate a new treatment for naturally acquired canine scabies. A liquid concentrate formulation of amitraz was diluted and applied as a sponge-on therapy. Ninety-four percent of the dogs treated with the scabicide were cleared of mites and returned to clinical normality with a single topical treatment; one dog was retreated, cleared of mites and was also returned to normality. All dogs treated with the miticide responded clinically, therefore the treatment also may be useful when trial therapy is necessary to differentially diagnose the disease. The miticide was well tolerated by all dogs, and there was no evidence of dermal or ocular irritation. Topical treatment with the liquid concentrate was efficacious and safe as a therapy for naturally acquired canine scabies. Placebo controls did not improve clinically and these animals retained their mite populations.

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Fifty-two dogs naturally parasitized with Demodex canis and having the generalized form of the disease were utilized to evaluate the efficacy and safety of single or multiple topical treatments with a liquid concentrate formulation of amitraz. Ten dogs (5 treated, 5 controls) were utilized to evaluate a single treatment. A single topical treatment with the miticide did not significantly reduce the incidence of dogs with mites, however, significant clinical improvement resulted. Side-effects were not observed after treatment. Forty-two dogs (26 treated, 16 controls) were utilized to evaluate multiple topical treatments with the liquid concentrate. A series of 3-6 treatments was applied topically at 14-day intervals. The dogs treated with the miticide received an average of 4.5 topical treatments. All (100%) of the dogs responded clinically, and the mean rate of improvement at four weeks post-treatment was 99.1%. Most dogs (96.2%) were cleared of mites after 3-6 treatments, and Mitaban did not cause any dermatologic, ocular, or other clinical side-effects. Multiple treatments with the liquid concentrate were highly efficacious and safe for treatment of generalized demodicosis. Control dogs did not improve clinically and retained mite populations.

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A new anthelmintic candidate, p-toluoyl chloride phenlylhydrazone, was administered to lambs in a paste formulation. The efficacy of this drug was determined at dose rates of 20, 30, 40, and 50 mg of active ingredient per kilogram of body weight. Helminths expelled by these dosages included Haemonchus contortus, Ostertagia circumcicta, Trichostrongylus colubriformis, T. axei, Nematodirus filicollis, Cooperia curticei, Strongyloides papillosus, Oesophagostomum columbianum, Bunostomum trigoncephalum, Chabertia ovina, Moniezia expansa, and M. benedeni.

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