The biochemical basis of anthelmintic action and resistance

The most commonly used modern anthelmintics include the benzimidazoles, the nicotinic agonists, praziquantel, triclabendazole and the macrocyclic lact ones. These drugs interfere with target sites: that are tither unique to th e parasite or differ in their structural features from those of the homolog ous counterpart present in the vertebrate host. The benzimidazoles exert th eir effect by binding selectively and with high affinity to the beta -subun it of helminth microtubule protein. The target site of the nicotinic agonis ts: (e.g. levamisole, tetrahydropyrimidines) is a pharmacologically distinc t nicotinic acetylcholine receptor channel in nematodes. The macrocyclic la ctones (e.g. ivermectin. moxidectin) act as agonists of a family of inverte brate-specific inhibitory chloride channels that are activated by glutamic acid, The primary mode of action of other important anthelmintics (e.g. pra ziquantel, triclabendazole) is unknown. Anthelmintic resistance is: wide-sp read and a serious threat to effective control of helminth infections, espe cially in the veterinary area. The biochemical and genetic mechanisms under lying anthelmintic resistance are not well understood, but appear to be com plex and vary among different helminth species and even isolates. The major mechanisms helminths use to acquire drug resistance appear to be through r eceptor loss or decrease of the: target site affinity for the drug. Knowled ge on the mechanisms of drug action and resistance may be exploitable for t he development of new drugs and may provide information on ways to overcome parasite resistance, respectively. (C) 2001 Australian Society for Parasit ology Inc. Published by Elsevier Science Ltd. All rights reserved.