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An in vitro screen for new fasciolicidal agents

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In vitro screens employing newly excysted, 6- and 12-week-old flukes, in a medium permitting the linear growth of the parasites, were assessed. When exposed to certain known fasciolicides, newly excysted flukes were susceptible only to diamphenethide, the free amine of diamphenethide, emetine hydrochloride and albendazole. Older flukes were affected by a much wider range of compounds including the chlorinated hydrocarbons, the substituted phenols and the salicylanilides. However their susceptibility to diamphenethide and its active metabolite was decreased significantly. The activity of fasciolicides in these in vitro assays therefore closely parallels their activity in vivo. When several broad spectrum anti-nematode agents were evaluated against newly excysted flukes in these screens the benzimidazole, isothiocyanate, pyrimidine and imidazothiazole anthelmintics showed activity but 12 potent antiprotozoal agents were all inactive. It is concluded that these in vitro assays were useful for detecting any intrinsic activity that a compound might possess against flukes. Such activity could often be missed in conventional in vivo screens because of problems associated with host pharmacokinetics. Negative results from such in vivo screens could preclude the development of more bioavailable derivatives or pro-drugs as novel and useful fasciolicidal agents.

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Ibarra, O.F., Jenkins, D.C. An in vitro screen for new fasciolicidal agents. Z. Parasitenkd. 70, 655–661 (1984).

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