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Pharmacology of Naphthoquinones

WITH SPECIAL REFERENCE TO THE ANTIMALARIAL ACTIVITY OF LAPINONE (WR 26,041)^*

Domingo M. Aviado AND Donald H. Will

Lapinone, chemically known as 2-hydroxy,3-(9-hydroxy-9-pentyltetradecyl) 1–4 naphthoquinone, has received the Walter Reed acquisition number of WR 26,041. In mice infected with Plasmodium berghei, 100 mg per kg of WR 26,041 was effective both subcutaneously and orally in suppressing parasitemia. In infected rats, 100 mg per kg administered subcutaneously, orally, or intraperitoneally also suppressed parasitemia and prolonged the duration of survival. In the rat, the intravenous lethal dose was about equal to the antimalarial dose. The cardiovascular effects of WR 26,041 were investigated in three species of animal. In the isolated rat atrial muscle, this compound exerted a quinidine-like action. In the cat, the intravenous infusion of WR 26,041 potentiated some actions of epinephrine, whereas in the dog, there was no depression of cardiac output. The effect of the compound on the mobility of erythrocytes was investigated as an initial step in the development of an in vitro test to assess antimalarial activity against P. berghei.

^* This study is contribution No. 425 from the Army Research Program on Malaria, and is based on work under Contract DA-49-193-MD-2755 by U. S. Army Medical Research and Development Command.

Formerly National Institutes of Health Postdoctoral Fellow; presently at the Department of Physiology and Biophysics, Colorado State University College of Veterinary Medicine, Fort Collins, Colorado.