@article {HATCHER385, author = {ROBERT A. HATCHER and CARY EGGLESTON}, title = {A CONTRIBUTION TO THE PHARMACOLOGY OF NOVOCAIN}, volume = {8}, number = {7}, pages = {385--405}, year = {1916}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {It is still commonly stated that the toxicity of novocain is about one-sixth to one-tenth that of cocain, even though several observers have called attention to the dependence of the toxicity of novocain on the mode of administration, and especially on the rapidity which which it enters the circulation. The toxicity of novocain is greatest when a concentrated solution is injected rapidly into the vein, in which case a dose of 40 mgm. per kilo is fatal to the cat and rabbit, and probably to other animals, though much smaller doses cause severe, and even threatening, symptoms. Very much larger doses may be injected slowly into the vein or subcutaneously without causing more than temporary disturbances. Cocain shows an analogous though slighter variation in toxicity dependent on the mode of administration. The subcutaneous injection of a mixture of novocain and epinephrin results in greatly delayed absorption and consequently diminished toxicity of the novocain for the cat. When such a mixture is injected intravenously there is a synergistic constrictor action on the vessels, with an antagonistic effect on toxicity probably due to the action of epinephrin on the heart. The toxicity of novocain is increased, but in a variable degree, by the previous administration of hydrated chloral which depresses the respiratory center. The extremes of toxicity of novocain shown when it is injected rapidly into the vein of a chloralized cat (10 mgm. per kilogram, fatal) and when administered slowly to a normal cat (408 mgm. per kilogram with only temporary disturbance) suggest a possible explanation of the accidents occasionally seen when small doses of novocain are used clinically. Novocain leaves the blood stream rapidly, being fixed or destroyed in the liver, the weight of evidence pointing to its destruction in that organ. Less than 3 per cent (if any) of a large intravenous dose is excreted unchanged in the urine of a cat within a period of two to three hours.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/8/7/385}, eprint = {https://jpet.aspetjournals.org/content/8/7/385.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }