INHIBITION OF SODIUM URATE-INDUCED RAT HINDPAW EDEMA BY COLCHICINE DERIVATIVES: CORRELATION WITH ANTIMITOTIC ACTIVITY

¹ Laboratory of Chemical Pharmacology and Experimental Therapeutics Branch, National Heart and Lung Institute, National Institutes of Health, Bethesda, Maryland
² Laboratory of Chemical Pharmacoogy and Experimental Therapeutics Branch, National Heart and Lung Institute, National Institutes of Health, Bethesda, Maryland

Colchicine, 17 of its derivatives and two other antimitotic compounds, podophyllotoxin and vinblastine, were examined for their ability to inhibit the edema induced in the rat hindpaw by subplantar injection of sodium urate crystals. Of these substances, demecolcine, colchiceinamide, trimethylcolchicinic acid methyl ether and trimethylcolchicinic acid ethyl ether were almost as effective as colchicine in inhibiting the edema. Podophyllotoxin and vinblastirie also suppressed most of the edema, whereas, N-desacetylthiocolchicine, colchiceine, N-acetylcolchinol, colchinol and N-acetyliodocolchinol had less inhibitory activity and the other eight derivatives were ineffective. When the anti-inflammatory results obtained with these compounds were compared to the in vivo antimitotic activity published by others, the same rank order of potencies was obtained. This correlation supports the hypothesis that a microtubule system is involved in both the antimitotic and anti-inflammatory actions of colchicine and its derivatives. Futhermore, our results suggest that analogs, such as colchiceinamide and trimethylcolchicinic acid methyl and ethyl ethers, may be as effective as, but less toxic than, colchicine in the therapy of gout.