The Toxicity of Nupercaine. ∗

Among the requirements of an ideal local anesthetic agent is prolongation of action. Attempts have been made to meet this requirement, especially in connection with quinine derivatives, but tissue injury at the site of injection has generally precluded clinical use of such agents. 1 Uhlmann 2 introduced the diethyl-ethylene-diamide of butyloxycinchoninic acid (nupercaine, N.N.R.). In Europe this drug came into immediate favor, but a number of deaths were reported 3 following its use. Papers on the toxicity of nupercaine have been published, 4 but since these are not in agreement and did not take up the question of protection, further study seemed indicated.

We began with a 1% solution of nupercaine, but due to tissue irritation, we changed to a 0.5% solution. Rabbits were used and the drug was given subcutaneously or intravenously, with or without protection. For protection we used paraldehyde administered in water emulsion by stomach tube.

Subcutaneous injection of nupercaine gave rise to convulsions on an average of 17 minutes from the time of injection. During this period there was first depression, then followed nervous excitement with loss of coordination, and finally clonic convulsions. Respiration became rapid, while the pulse was slow and irregular. Those animals recovering took 2 to 3 hours before they seemed normal. In those that died, the respiration stopped a few seconds before the pulse. The lethal dose (LD₅₀) of 8.5 mg./kg. is one-twelfth of the minimal lethal dose for cocaine given subcutaneously as reported by Knoefel, Herwick, and Loevenhart. 5

Rabbits receiving an intravenous lethal dose of nupercaine died in less than a minute, and usually without any muscular effect whatever, although some had one severe convulsion. Kymographic studies indicated that nupercaine is similar in action to cocaine on intravenous administration in lethal doses. 5