THE IN VITRO EFFECT OF AGRIMOPHOL ON SCHISTOSOMA JAPONICUM

Agrimophol, an active principle of Agrimonia pilosa Ledeb, exhibited a direct and strong in vitro action against Schistosoma japonicum, when bisexual worms collected from infected rabbits were maintained in a culture medium containing 4μg/ml of agrimophol. A stimulation of worm activity appeared within 4 minutes followed by a spasmodic contraction of schistosome musculature. Meanwhile, the worms remained motionless except a feeble motion of the oral sucker.The survival time of the worms was markedly reduced by agrimophol at the concentration of 0.5～2μg/ml. When bisexual worms were exposed to 8 or 16μg/ml for 24 hours, and then transferred to a drug-free medium, all of the worms could not recover from their motionless state and eventually died in 3～7 days.The action of agrimophol on the worms was not antagonized by atropine nor 5-hydroxytryptamine. Histochemical studies revealed that agrimophol exhibited no effect on the acetylcholinesterase activity of the worms.Ithas been found that when schistosomes were exposed in vitro to 8 μg/ml of agrimophol for 15 minutes daily for 8 days, the worms became less sensitive to the drug after the second exposure, resulting in an apparent prolongation of the time for the worms to become motionless.After oral adminstration of agrimophol 300 mg/kg/day×5 combined with oral niridazole 75 mg/kg/day×5 to infected mice, a hepatic shift of the worms was observed. After the worms were perfused out from the liver and maintained in a drugfree medium, all of them could not recover their normal activity. Nosynergistic action was observed when schistosomes were exposed directly to a culture medium containing both drugs.