EFFECT OF A PAIR OF ENANTIOMERS WITH LOCAL ANESTHETIC ACTIVITY ON ACTION POTENTIAL GENERATION AND ACETYLCHOLINE SENSITIVITY IN MUSCLE

The enantiomers of N-(γ-diethylaminopropyl)- 1,2,3,4-tetrahydronaphtalin-spirosuccinimide), a member of a new class of local anesthetics,were investigated with reference to their ability to block (1) action potential generation and (2) chemical sensitivity in muscle. The enantiomers were equally effective in blocking the effect of acetylholine, nicotine and histamine in guinea-pig ileum and the response of the frog rectus abdominis to applied acetylcholine. There was no difference in their ability to block membrane potential change due to ionophoretically applied acetylcholine in denervated rat extensor. The suggestion is made that local anesthetics may produce their effect on chemical sensitivity not by affecting the chemically sensitive site, but by blocking the sites of ion transfer secondary to chemical sensitivity. In blocking electrically induced action potential generation, enantiomer I was always more effective than enantiomer II supporting the view that steric interaction of drug with site of action is of significance in block of electrical excitability. The findings to support the concept that the mechanism of ion flow initiated by acetylcholine is somewhat different from that of the action potential. © 1969.