A COMPARISON OF THE RELATIVE TOXIC, EMETIC AND CONVULSIVE ACTIONS OF A SERIES OF METHYLATED XANTHINE DERIVATIVES

¹ Department of Pharmacology, University of Toronto, Toronto, Canada

The acute intraperitoneal and oral toxicity in terms of LD₅₀ mgm./kgm. was determined in the mouse for a series of 1 and 7 substituted xanthines.

The values calculated for the LD₅₀ by the intraperitoneal route in terms of mgm./kgm. varied from 100 to 1800. 1-Allyl theobromine was the most toxic derivative while 7---dihydroxypropyl theophylline was the least toxic.

By the oral route, the values for the LD₅₀ in terms of mgm./kgm. varied from 190 to 2700. Again 1-allyl theobromine was the most toxic while 7-acetic acid theophylline was the least toxic.

7-Diethylaminoethyl theophylline was the most active derivative in producing convulsions in the mouse. Convulsions were also observed with 7-isoamyl theophylline, 7-butyl theophylline, caffeine, theophylline, aminophyffine, 1-butyl theobromine and 7-chloroethyl theophylline.

By oral administration theophylline and aminophylline were well tolerated in both the dog and the cat. In both species, 1-butyl, 1-isoamyl theobromine, 7-acetic acid and 7-isoamyl theophyffine were the most active of these derivatives in producing emesis. 7-Diethylaminoethyl theophylline caused fatalities in both the dog and the cat.

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