A Screening Procedure for Substances Which Inhibit Dextran Edema in the Rat

¹ From The Wm. S. Merrell Company, Cincinnati, Ohio

Determination of foot volume by mercury displacement before and after the intraperitoneal administration of dextran to rats demonstrated that pronounced edema occurs one-half to three-fourths of an hour after dextran, reaches a maximum in 1 1/2 hours, and gradually subsides over the next several hours. Inhibiting substances prevent the edema entirely, reduce its severity or delay its appearance. A method was presented for screening compounds for ability to inhibit dextran edema. A dose-response curve developed for chlorpromazine suggests that the technique might also be suitable for quantitative bioassay. It was found that strongly vasoconstrictor adrenergic agents inhibited edema while adrenergic drugs with other predominating activities did not. Atropine, Dibenamine, morphine, reserpine, hydroxyzine and meprobamate were inactive. Chlorpromazine, the antihistaminics and anesthetic doses of phenobarbital were active. Cortisone and phenylbutazine were inactive but the salicylates were moderately active.