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The effect of albendazole and triclabendazole on colchicine binding in the liver fluke Fasciola hepatica
Author(s) -
FETTERER R. H.
Publication year - 1986
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1986.tb00011.x
Subject(s) - fasciola hepatica , triclabendazole , anthelmintic , colchicine , albendazole , liver fluke , in vivo , mebendazole , benzimidazole , pharmacology , biology , chemistry , microbiology and biotechnology , helminths , immunology , ecology , genetics , organic chemistry
Albendazole (ABZ) and its sulfoxide (SX) and sulfone (SO) metaliolites inhibit the binding of :3 H‐colchicine, a ligancl with high affinity for tubulin to homogenate preparations of the liver fluke Fasciola hepatica. The relative potency of these compounds is SX > ABZ > SO. The benzimidazoles (cambendazole, parbendazole, oxibendazole and mebendazole), when tested at a concentration of 10 μM, also inhibited colchicine binding to fluke homogenates. However, a potent new benzimidazole flukacide, triclalbendazole (TCB), was without effect on colchicine binding to F hepatica homogenates. When intact flukes were exposed in vivo to 10 ‐5 ′M SX for as little as 5 min the subsequent binding of 3 H‐colchicine to fluke homogenates was significantly reduced. However, flukes recovered from sheep either 12 or 24 h after treatment with ABZ did not have a decreased ability to bind colchicine, although the non‐specific binding was higher in flukes from treated sheep, suggesting some interaction of drug with tubulin in vivo. ABZ, SX and SO were effective in preventing embryonation of lluke eggs at doses as low as 0.0 1 μM, but TCB was without effect at concentrations as high as 10 μM. The results suggest that ABZ exerts at least part of its anthelmintic effect by interaction with fluke tubulin.