Isonipecaine, an isonipecotic acid derivative (l-methyl-4-phenylpiperidine-4-carboxylic acid ethyl ester hydrochloride), was found to possess considerable local anesthetic properties. I n the discussion of the results, the structural relationships of isonipecaine are compared with those of atropine, cocaine, and morphine. Suggestions of a speculative nature are made which deal with its possible use against cardiac arrhythmias, and with possible methods for treating and prebenting isonipecaine toxicity.
INCE its introduction by Eisleb and Schaurnann (l), the isonipecotic acid derivative, isonipecaine (ethyl ester of 1methyl-4-phenylpiperidine-4-carboxylic acid hydrochloride), known also as demerol, dolantin, pethidine, eudolat, meperidine, etc., has proved to be a valuable therapeutic agent. Pharmacological studies thus far reported on the compound (1-5), indicate that it possesses a wide range in activity, being analgetic, spasmolytic, and sedative.
During the investigation of'some of the effects of isonipecaine, it was noted that the compound produced pronounced corneal anesthesia when applied to the rabbit eye. Although isonipecaine has been reported to abolish the corneal reflex (2, G ) , the effect was produced after systemic administration. The action we obtained was essentially a local one, and was not due to the central actions of isonipecaine.
In 1940 Schaumann (2) observed that isonipecaine produced a slight anesthetic effect on the mucous membrane of the mouth. He apparently considered this local effect to be insignificant because when he instilled 1 per cent isonipecaine into the cat eye, he noted only slight midriasis and did not test for corneal anesthesia. Also, after he observed that isonipecaine intravenously potentiated the local effects of procaine on the rabbit eye, he did not investigate the possibility that isonipecaine locally might produce corneal anesthesia.