Local Anesthetic Activity and Acute Toxicity of N-Heptyl-1,2,3,4-tetrahydro-6-rnethoxy-1-naphthylamine Methanesulfonate

N-Heptyl-1,2,3,4-tetrahydro-6-met,hoxy-1-naphthylamine methanesulfonate (I) is a potent, long lasting local anesthetic. It was as potent as tetracaine and at least 10 times more potent than lidocaine in the rabbit corneal reflex, guinea pig wheal, and mouse sciatic nerve block tests. The threshold anesthetic concentration (TAC), defined as the concentration required to produce anesthesia lasting 5 min, was calculated from each linear regression line fitted to the log dose-duration data, and these values were used to compare the potencies of the local anesthetics. In the rabbit corneal reflex test, the TAC values were 0.04% for I. 0.04% for tetracaine, and 0.66% for lidocaine. In the guinea pig wheal test, I had a TAC of 0.02%, which was equipotent to tetracaine and 11 times more potent than lidocaine; epinephrine (1:100,000) prolonged the duration of action of all three local anesthetics but had the least effect with I. In the mouse sciatic nerve block test, the TAC values were 0.06% for I, 0.10% for tetracaine, and 0.86% for lidocaine. The acute LDm values of I in mice were 138mg/kg sc and 26mg/kg iv. By either route, I was less toxic than tetracaine and more toxic than lidocaine. Comparison of the LD50 and TAC values in the mouse sciatic nerve block test indicated that I had a greater therapeutic index than either reference standard.