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1 Department of Pharmacology, Cornell University Medical College, New York, New York
The effects of four local anesthetics, procaine, lidocaine, tetracaine and dibucaine, were studied on the soleus neuromuscular preparation of the cat in vivo. All local anesthetics injected i.a. or i.v. depressed the posttetanic potentiation of the soleus muscle and abolished the neural repetitive afterdischarge of the motor nerve terminals. In addition, local anesthetics modified the pattern of tetanic muscle contraction. Lidocaine was 1.5, tetracaine was 10 and dibucaine was 15 times more potent than procaine in depressing posttetanic potentiation. Recovery of posttetanic potentiation (PTP) was rapid following procaine and lidocaine, but it was prolonged after tetracaine and dibucaine administration. Since PTP and posttetanic repetitive activity are neural events and local anesthetics depressed them without depressing the transmission of single twitches, it is concluded that local anesthetics act by selective depreseion of the motor nerve terminal. The correlation between drug potencies for PTP suppression and local anesthetic potency for blocking conduction in peripheral nerves and the agreement between doses depressing PTP and those affecting central nervous system neurons also support a neural locus of action. The possibility of a postjunctional effect of local anesthetics is considered, but, according to the dose-response relationship, it only occurs after the injection of larger doses.
Submitted on June 26, 1967
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