Anthelminthics benzimidazoles

The benzimidazole group of anthelminthics is derived from the simple benzimidazole nucleus and includes the thiabendazole analogues and the benzimidazole carbamates. Substitution of side chains and radicals on the benzimidazole nucleus gives rise to the individual members of this group (Fig. 4.1). 

A number of benzimidazoles exist as prodrugs their anthelminthic activity is due to the fact that they are metabolized in the animal body to the biologically active benzimidazole carbamate nucleus. Due to their relatively slower excretion rates, the newer insoluble benzimidazoles have fairly long withdrawal periods for edible tissues and milk in contrast to the less effective and more rapidly excreted thiabendazole analogues. Strict compliance with withdrawal periods is always necessary because of the potentially toxic and teratogenic effects of some of the benzimidazoles and their metabolites. 

Parbendazole is an old anthelminthic that has been widely used against gastrointestinal nematodes and lungworms in cattle, sheep, and swine at dosages in the range 15-50 mg/kg bw. It is the drug in which the teratogenic effects of benzimidazoles were first identified. 

Three classes of anthelminthics were also monitored macrocyclic lactones, benzimidazoles, and levamisole. Samples were taken from cattle, sheep, pigs, and ostriches. Only 2 of 2613 samples contained residues above the MRL. These were for fenbendazole in a cattle sample and avermectin in a sheep sample. 

Since all members of the benzimidazole anthelminthics except thiabendazole contain a benzimidazole carbamate moiety, attempts have been made to produce antibodies recognizing this structure (19). Most successful was an approach in which a carboxylated analogue of albendazole was used as hapten and coupling to the carrier protein was performed using (V-hydroxysuccinimide and morpholi-noethyl isocyanide in the presence of dimethylamino pyridine. 

However, the vinylogy principle is sometimes applied to the design of bioisosteres. Thus the guanidinic group of the benzimidazole fenbendazole can be compared with its vinylogue in the corresponding imidazo[l,2-a]pyridine (Fig. 12.31). Both compounds are anthelminthics of similar potency. 

Samsoniya, Sh. A. Zurabishvih, D. S. Lomidze, M.O Chitiashvili, B.G. Sadaterashvili, I.F. Synthesis and anthelminthic activity of 5(6)-(l-adamantyl)benzimidazole. Chemistry and technology of frame compounds IX International scientific Conference. Russia-Volgograd -2001,193-194. 

Lomidze, M. Gogolashvili, I. Barbakadze, Kh. Zurabishvih, D. Sadaterashvili, I. Chitiashvili, B. Skhirtladze, S. Napetvaridze, N. Kvachadze, M. Sadaterashvili, G. Synthesis and study comparative anthelminthic activity of adamantane-containing amines, amides and benzimidazoles. International scientific Conference. Advances of Chemistry and Applications of Alicyclic Compounds, Russia - Samara 1-4 of June, 2004.P.178... 

Chitiashvil, B. Skhirtladze, S. Napetvaridze, N. Synthesis and study of anthelminthic activity of adamantane derivatives. Report II. Synthesis and screening of 5(6)-(l-adamantyl)-benzimidazole at experimental syngamosis and ascaridiasis in hens. Georgian State Zootechnical-Veterinary University, collected scientific works, vol. LXIV, 407-412, Tbilisi, 2004. 

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