| Abstract: | The cyclic depsipeptide PF1022A, given orally to mice, showed very good anthelmintic activity against Heligmosomoides polygyrus and Heterakis spumosa at 50 mg kg−1. In vitro, PF1022A was very active against Trichinella spiralis and had good activity against Nippostrongylus brasiliensis at 1 μg ml−1. An 18-membered enniatin analogue, JES 1798, showed good activity only against N. brasiliensis at 10 μg ml−1. The optical antipode of PF1022A had poor activity even at 100 μg ml−1. The effects of PF1022A on the membrane potential and input conductance of somatic muscle of Ascaris suum 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 Cl− ions. The addition of high concentrations of Ca2+ to the preparation after the addition of PF1022A did not lead to production of Ca2+-activated Cl− channels, suggesting that its mode of action was not that of a Ca2+ ionophore. The mechanism by which the cyclic depsipeptide might increase the Cl− conductance is discussed. |
