The interactions between drugs and the parasite surface

Abstract

SUMMARYThe interrelationships between drugs and parasite surfaces are considered under the headings of (a) effects on membrane transport, (b) drug uptake mechanisms and (c) effects on surface morphology and function: praziquantel is discussed under a separate heading. The range of chemotherapeutic compounds that cause permeability changes and concomitant morphological disruption is discussed in terms of mode of drug action. Interpretation of the available data renders it difficult to identify the primary mode of action in the drugs considered. Drug uptake mechanisms are known for relatively few compounds; drug resistance as a function of drug acquisition is discussed. The role of the parasite surface as a specific drug target is argued.

Praziquantel treatment of Biomphalaria glabrata infected with Schistosoma mansoni– influence on snail fecundity

“…Perhaps a total elimination of the parasite would have enabled recovery in all the groups of snails. Although the mode of action of praziquantel remains unclear it acts at the membrane level altering the Ca 2+ flux and affecting surface membrane potential (reviewed by Chappell, 1988). It is interesting and currently unexplained that this drug, known to be active against adult worms (Gonnert & Andrews, 1977), eggs (Richards et al 1989), miracidia and cercariae (Andrews, 1978), is without effect on the daughter sporocysts of S. mansoni at the dose levels employed.…”

Effect of praziquantel on the strobilar development of Mesocestoides corti in vitro

“…particular, is the drug of choice for the treatment of a wide range of veterinary and human helminthic infections. It has proved to be highly effective against adult worms but less so against larval forms (Heath & Lawrence, 1978;Andrews & Thomas, 1979;Thompson et al, 1986;Chappell, 1988).…”

“…Over the last decades, parasite chemotherapy has attracted considerable attention and extensive information is available about the chemistry and mode of action of many anthelmintic drugs. Moreover, their effects on distinct developmental stages of several helminth species in in vivo and in vitro systems have been described (Thomas & Gonnert, 1978;Andrews & Thomas, 1979;Thompson et al, 1986;Morris et al, 1987;Chappell, 1988). Little has been analysed, however, about their incidence on differentiation processes leading from one developmental stage to another.…”

In vitro taurocholate-induced segmentation and clustering of Mesocestoides vogae (syn. corti) tetrathyridia (Cestoda) – inhibition by cestocidal drugs

“…However, most currently used anthelmintics have very poor cestocidal activity. At least partially, this may be the result of drugs being mainly tested against nematode and trematode model organisms, both in vitro and in vivo (Chappell 1988;Coles 1990;Lima et al 1994;Martin 1997), rather than against cestode organisms for that purpose (Dixon and Arai 1991;Kaur et al 1995).…”