PT  - JOURNAL ARTICLE
AU  - OTTO FÜRTH
AU  - ERWIN KUH
TI  - BIOCHEMICAL STUDIES ON THE ABSORPTION OF THE ETHYLESTER OF PARAMETHYLPHENYLCINCHONINIC ACID (TOLYSIN) AND ITS FATE IN METABOLISM II. THE FATE OF TOLYSIN IN METABOLISM AND ITS TOXICITY
DP  - 1930 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 71--84
VI  - 38
IP  - 1
4099  - http://jpet.aspetjournals.org/content/38/1/71.short
4100  - http://jpet.aspetjournals.org/content/38/1/71.full
SO  - J Pharmacol Exp Ther1930 Jan 01; 38
AB  - The ratio of absorption of Cinchophen and Tolysin was controlled by its depressing effect on the temperature of normal and coli-fever animals and by its toxicity. In a rabbit 0.9 gram Cinchophen per kilogram per os induced transient paralysis of the hind legs and 1.0 per kilogram caused death.—With Tolysin in normal rabbits 1.0 gram per kilogram induced a marked fall of temperature, 1.2 gram severe intoxication and 1.4 grams death. (This ratio corresponds to the clinical experiences about the relative amounts of Tolysin and Cinchophen wanted in acute rheumatic fever for securing a complete relief.) In a rabbit suffering from coli-fever 0.4 to 0.5 gram Tolysin per kilogram per os have been fully sufficient for producing a very marked decrease of temperature. Of course the absorption of Tolysin from the intestine seems somewhat slower than the absorption of Cinchophen. Contrary to the absorption from the gastro-intestinal tract, the absorption of Tolysin in olive oil solution from the subcutaneous tissue is indeed a very poor and slow one. As for the fate of Tolysin in the intermediate metabolism the bulk is destroyed by the catabolizing agents of the living organism. After having administered to rabbits Tolysin (about 1 gram in 10 per cent olive oil-solution by way of the pharyngeal sound daily) several percents of the ingested compound used to appear in the urine in the shape of a substance of distinctly acid character, soluble in alkali and precipitated by acid and soluble in organic solvents. From the alcoholic solution it is thrown down by cadmiumchloride in a crystalline form. The pure substance has a marked orange colour and is characterized by a brilliant diazo-reaction. This substance, which has been separated from the urine in shape of fine crystalls and in a pure state, may be considered as a Dioxymethylphenylquinolincarboxylic acid or Dioxymethylcinchophen C17H13NO4. Of the 4 atoms of O two are contained (as titration shows) in one carboxylic radical. The two others are to be found in two hydroxyl groups, inasmuch the determination according to Zerewitinoff with a Grignard-reagent reveals the presence of 3 active hydrogen atoms within the molecule.