Extracts of ground seeds from Annona squamosa revealed interesting insecticidal properties. By an activity‐monitored fractionation, different acetogenins, called annonins and annonacin, were determined to be the active components. The investigation of ATP‐levels (at the LT50 value) in Plutella xylostella under treatment with annonin I and antimycin A revealed values of 1.45 and 1.35 μmole g−1 fresh weight respectively, whereas insecticides primarily afecting neurotoxic targets, e.g. cyfluthrin (sodium channels; 2.25 μmole g−1 fresh weight) or parathion (acetylcholinesterase; 2.0 μmole g−1 fresh weight) did not influence the ATP‐levels significantly (control; 1.98 μmole g−1 fresh weight). Further studies on the target site of annonins revealed an inhibitory effect on the NADH‐cytochrome c‐reductase and complex I of insect mitochondria with IC50 values of 4–8 nmole mg−1 protein and 0.8 μM respectively for annonin I. Similar results were observed for the inhibition of complex I from bovine heart muscle (IC50: <0.1 μM) or Neurospora crassa cells (IC50: 0.3 μM), whereas coupling sites II or III were not afected. Furthermore, annonins did not reveal any direct inhibition of oxidative phosphorylation or uncoupling efects.

Intensive use of parasiticides has sometimes led to severe resistance in arthropods and helminths of veterinary importance. In the context of the growing awareness of parasitic diseases, this has created a public demand for effective and safe control agents. During the last two decades considerable knowledge in parasite neurophysiology and endocrinology has accumulated which allows the development of new screening procedures and target‐site‐directed approaches for the discovery of new drugs. The suitability of this strategic approach is discussed on the basis of recent discoveries of new chemical and natural compounds. In particular, target sites such as GABAA receptors, muscarinic and nicotinic acetylcholine receptors, cuticle synthesis and degradation, ecdysteroid receptors, the calcium release channel and semiochemicals have been selected in order to demonstrate the current approaches to identify new chemical entities, biologically active against nematodes and arthropods.

Chitin is an important component of the exoskeleton of arthropods and of the egg shell in nematodes, but it does not occur in vertebrates. Therefore, it represents a useful target for drugs against ectoparasitic crustaceans, insects and endoparasitic nematodes. In this review we describe the basic characteristics of chitin, chitin synthesis and degradation and the hormonal regulation of chitin metabolism. Substances interfering with chitin metabolism like benzoylphenyl-urea derivatives but also some recently detected compounds are described. The necessity for a more detailed understanding of chitin metabolism and the establishment of better model systems, like e.g. chitin producing insect cell lines, is stressed and some examples are given in this review.

A GC-MS method capable of completely separating the four pairs of diastereoisomers of cyfluthrin is presented and the method used to show that isomerisation of the cyfluthrin enantiomers occurs in methanol. This methanolinduced isomerisation could also be demonstrated by bioassays using water fleas. The biological activities of the various cyfluthrin isomers contained in the commercial products cyfluthrin and beta-cyfluthrin were assayed using several strains of lepidopteran larvae including Plutella xylostella, Heliothis virescens and Spodoptera frugiperda. With the susceptible strains, the efficiencies of the isomers mixtures of cyfluthrin and beta-cyfluthrin were shown to obey the rules of additivity. However, in tests with a resistant strain of P. xylostella originating from Thailand, the 'inactive' isomer I11 acted synergistically with the active isomer IV.Resistance factors in strains of H. virescens and P. xylostella were found to be higher with cis than with trans isomers. This probably contributes to the superior action of cyfluthrin and beta-cyfluthrin against various pests of agricultural importance since the commercial products contain a high content of trans isomers ('high trans pyrethroids').

The cyclic depsipeptide PF1022A, givea orally to mice, showed very good anthelmintic activity against Heligmosomoides polygyrus and Heterakis spwnosa at 50 mg kg-'. In uitro, PF1022A was very active against Trichinella spiralis and had good activity against Nippostrongylus brasiliensis at 1 pg d-'.An 18-membered enniatin analogue, JES 1798, showed good activity only against N . brasiliensis at 10 pg d-'. The optical antipode of PF1022A had poor activity even at 100 pg d-l. The effects of PF1022A on the membrane potential and input conductance. of somatic muscle of Ascaris mum were examined using a two-microelectrode current-clamp technique. PF1022A did not antagonize the effects of the selective nicotinic agonist levamisole. PF1022A and an analogue, JES 1798, but not the PF1022A antipode, produced a small time-dependent increase in input conductance associated with no potential change. The increase in input conductance did not occur in the Cl--free bathing solution, suggesting that the increase in input conductance was mediated by C1-ions. The addition of high concentrations of Ca2+ to the preparation after the addition of PF1022A did not lead to production of CaZ +-activated C1-channels, suggesting that its mode of action was not that of a Ca2+ ionophore. The mechanism by which the cyclic depsipeptide might increase the C1-conductance is discussed.