Anthelmintics, used for the treatment of fascioliasis as uncouplers of oxidative phosphorylation in warm blooded animals

The pharmacodynamics of the flukicidal salicylanilides, rafoxanide, closantel and oxyclosanide

“…The salicylanilides are known to be uncouplers of oxidative phosphorylation in mammals (Williamson & Metcalf, 1967;van Miert & Groeneveld, 1969) and in liver fluke (Cornish & Bryant, 1976;Prichard, 1978). It might be expected that, as flukes mature and move from more anaerobic conditions in liver parenchyma to more aerobic conditions in bile ducts, the increased efficacy of uncouplers of oxidative phosphorylation against mature flukes would be explained.…”

Pharmacokinetic Data of Bromofenofos in Calves

“…The metabolite DBF is a substituted phenol, as nitroxynil, niclofolan, bithionol and hexachlorophene, which act as uncouplers of oxidative phosphorylation in both F. hepatica and mammals (MIERT and GROENEVELD, 1969;BARRAGRY, 1984). Moreover, BF was reported as an active uncoupler of oxydative phosphorylation in rats after oral administration (MIERT and GROENEVELD, 1969). These observations suggest that BF may act as an uncoupler of oxidative phosphorylation in F. hepatica rather than as cholinesterase inhibitor.…”

“…It was assumed that BF was rapidly and extensively hydrolyzed to DBF in the gastrointestinal tract in rats after oral administration (YOSHIMURA and ENDOH, 1989) and it is probable that this is also the site of BF metabolism in calves. The metabolite DBF is a substituted phenol, as nitroxynil, niclofolan, bithionol and hexachlorophene, which act as uncouplers of oxidative phosphorylation in both F. hepatica and mammals (MIERT and GROENEVELD, 1969;BARRAGRY, 1984). Moreover, BF was reported as an active uncoupler of oxydative phosphorylation in rats after oral administration (MIERT and GROENEVELD, 1969).…”

Progress in the Experimental Chemotherapy of Helminth Infections; Part I, Trematode and Cestode Infections

“…Hexachlorophene increases ATPase activity of liver mitochondria and causes a contraction of striated muscle in vitro. It is postulated [198], as a result of these findings, that the compound is a potent uncoupler of oxidative phosphorylation in warm-blooded animals. Recently, it has been confirmed that the fasciolicidal effect of hexachlorophene is due to uncoupling of oxidative phosphorylation in the parasite [199,200].…”

“…It has been demonstrated that 24 hours after administration of menichlopholan to sheep, serum glutamic-oxaloacetic transaminase levels markedly increased, then gradually returned to normal [206]. In common with hexachlorophene and several other halogenated phenols, menichlopholan uncouples oxidative phosphorylation in warm-blooded animals [198] : it is probable that the compound's mode of action in flukes is due to the same effect, although this does not appear to have been determined to date. References to menichlopholan in recent volumes of Chemical Abstracts appear under 5,5'-dichloro-3,3'-dinitro-2,2'-biphenyldiol and also (incorrectly) under 3,3'-dichloro-5,5'-dinitro-2,2'-biphenyldiol.…”