Haloxon

Binding sites on acetylcholinesterase for reversible ligands and phosphorylating agents. A theoretical model tested on Haloxon and phosphostigmine

Biochem Pharmacol 1984 Feb 15;33(4):671-7.6704184 10.1016/0006-2952(84)90324-1

The reaction of acetylcholinesterase (EC 3.1.1.7; human erythrocytes) with phosphostigmine, Haloxon and VX was studied, and the effect of three reversible ligands (TMA, edrophonium, coumarin) and of acetylthiocholine upon the time-dependent and time-independent (reversible) inhibition by the organophosphates was evaluated. The three ligands and acetylthiocholine decreased the second-order rate constant of phosphorylation by a factor proportional to the enzyme-ligand dissociation constant, or to both Km and Kss (Michaelis constant and the substrate-inhibition constant for acetylthiocholine) irrespective of the organophosphate. However, the time-independent inhibitions by phosphostigmine and Haloxon were differently affected. Acetylthiocholine affected the time-independent inhibition by phosphostigmine by a factor proportional to Km, and that by Haloxon by a factor proportional to Kss. Coumarin had no effect on the time-independent inhibition by phosphostigmine, while TMA and edrophonium displaced phosphostigmine from its complex. Coumarin displaced Haloxon from its complex with the enzyme, while TMA and edrophonium had no effect. We conclude that phosphostigmine and Haloxon bind reversibly to different sites on the enzyme and the experiments agree with a theoretical model that Haloxon binds reversibly to a peripheral site on acetylcholinesterase, and phosphostigmine to the catalytic site.

Toxicity of Haloxon in sheep

N Z Vet J 1966 May-Jun;14(5-6):71-2.5222053 10.1080/00480169.1966.33636

Haloxon: critical tests of antiparasitic activity in equids

Am J Vet Res 1981 Jun;42(6):1043-5.7283234

Critical tests were conducted in 14 naturally infected equids (13 horses and 1 pony) to evaluate the antiparasitic activity of Haloxon. Single doses were administered by stomach tube to 3 horses and 1 pony (60 mg/kg of body weight), by addition to the feed of 3 horses (60 mg/kg), and intraorally by powder gun to 7 horses (65 mg/kg). Haloxon was efficacious (99% to 100%) against infections of Parascaris equorum, Oxyuris equi (mature and immature), and Strongylus vulgaris at both dosage levels. Probstmayria vivipara parasites were removed in 1 horse treated at 60 mg/kg by stomach tube and S equinus was removed (1 specimen) in 1 horse treated at 65 mg/kg with the powder gun. Removal activity against small strongyles varied from 67% to 92%, and averaged 88% in ther aggregate. Removal of S edentatus fluctuated from 2% to 100%, and was 49% in the aggregate. Haloxon was generally ineffective against Gasterophilus intestinalis and G nasalis, except that it seemed active against 2nd instar G intestinalis when administered at the 60 mg/kg dosage rate in feed and at the 65 mg/kg dosage rate by powder gun. The compound was inactive against Trichostrongylus axei, Habronema muscae, Draschia megastoma, Anoplocephala perfoliata, and A magna. Clinical signs of toxicosis were not observed after treatment. Problems were not encountered in administration of Haloxon directly into the back of the mouth with the powder gun.

Efficiency and toxicity of Haloxon as an anthelmintic for sheep in Australia

Aust Vet J 1967 May;43(5):166-70.6067861 10.1111/j.1751-0813.1967.tb04829.x

Influence of plasma A esterase on anthelmintic action of Haloxon in sheep

Am J Vet Res 1980 Nov;41(11):1854-6.7212415

Controlled trials were conducted to evaluate the anthelmintic action of Haloxon in 2 phenotypes of lambs, 1 having an A esterase in plasma which rapidly hydrolyzes di-(2-chloroethyl)aryl phosphates and the other without this enzyme. A total of 116 lambs, 57 with and 59 without the plasma A esterase, 6 to 9 months old, harboring naturally acquired nematode infections were used in 3 trials. Haloxon was administered orally at 20, 25, and 35 mg/kg of body weight. Nematodes against which Haloxon was evaluated in the abomasum were Ostertagia circumcincta and Trichostrongylus axei and in the small intestine were T vitrinus, T colubriformis, Nematodirus spathiger, and N filicollis. The anthelmintic efficiency of Haloxon did not differ in the 2 phenotypes of sheep.