Antimalarial effect and toxicity of methyldihydro-artemisinine in animals

Methyl-dihydro-artemisinine (artemether) possessed higher efficacy against both Plasmodium berghei (both chloroquine sensitive and resistant strains) and P. cynomolgi than its parent compound, artemisinine. The resistance index=1.7. The factors affecting the antimalarial effect: 1) The tea seed oil preparation was better than the tragacanth gum suspension; 2) Using oil preparation, intramuscular administration gave a better result than intragastric administration; 3) The therapeutic effect was better by dividing same dose into 3-4 times within 3-4 days than once, twice or five times. Toxicity experiments included acute toxicity in mice, rats, rabbits, dogs and monkeys, and subacute toxicity in dogs and monkeys The observed items in subacute toxicity included general appearance, biochemical examinations, ECG, routine tests of blood and urine, and histological examinations. The results showed that its toxicity was lower than that of chloroquine, thus giving a broader safety margin for artemether although there were some loss of body weight and slight damage of liver parenchymal cells in the group dosing 36 mg/kg once for 3 months. There was no irritant reaction at the site of im injection. Alpha-Propoxy-carbonyl-dihydro-artemisinine (SM242) and alpha-propionyl-dihydro-artemisinine (SM108) were more potent than artemether against both P. berghei and P. cynomolgi, but their syntheses were more difficult and solubility in oil were lower than artemether.