Nodulisporic acid A (NSA) is a novel natural product from a new structural
class that was shown previously to have insecticidal activity against blowf
ly larvae. To determine if there was useful systemic efficacy against fleas
(Ctenocephalides felis), NSA was evaluated in an artificial membrane flea
feeding device and in dogs. In the artificial membrane flea feeding device,
adult C. felis were allowed to feed on bovine blood containing various con
centrations of NSA through a Parafilm membrane. NSA killed the fleas with a
50% lethal concentration of 0.68 mug/ml and was approximately 10-fold more
potent than the systemic insecticide ivermectin. In the initial probe dog
test, a single beagle was challenged with 100 C. felis before oral dosing w
ith 15 mg/kg of NSA. Flea counts conducted at 72 hr postdosing showed an 88
% reduction relative to control. Rechallenge of the same dog at 5 days post
dosing showed 50% reduction of fleas at day 7, demonstrating some residual
flea activity. In a confirmatory study, 8 dogs were challenged with 100 fle
as just before oral dosing with 15 mg/kg of NSA (4 dogs) or vehicle (4 dogs
). There was 99% reduction of fleas at 48 hr postdosing in the NSA-treated
dogs relative to control, Additional challenges with 100 fleas were perform
ed on these 8 dogs at 48-hr intervals to determine the duration of efficacy
, and there was 97, 51, and 0% reduction of fleas relative to control on da
ys 4, 6, and 8, respectively. No adverse effects were observed in the dogs
in these studies. These data show that NSA has potent oral activity in the
dog for the control of fleas, while lacking overt mammalian toxicity.