Carbamazepine suppression of post-tetanic potentiation at the neuromuscular junction

N Hershkowitz, KL Dretchen and A Raines

The effects of carbamazepine (CBZ) on post-tetanic potentiation (PTP) were evaluated using an in vivo cat coleus neuromuscular preparation. CBZ was administered i.p. and plasma CBZ concentrations were determined by gas liquid chromatography during PTP tests over a 90-min period. CBZ produced a concentration-dependent depression of PTP. Significant depression was first noted at about 12 microgram/ml and 50% depression occurred at 20 microgram/ml; this depression was time-dependent. No effect was observed on unpotentiated, supramaximal twitches. CBZ also modified the pattern of tetanic contraction; the most predominant change was an enhancement of the initial falling phase of the tetanus. Antidromically propagated post-tetanic repetitive afterdischarges (PTR) were monitored in single isolated vertral root filaments innerving the soleus muscle. CBZ inhibited PTR without affecting conduction velocity or the capacity of the fiber to follow the high frequency (tetanic) stimulation. These results are similar to those previously reported for phenytoin. CBZ inhibits PTP in this preparation by inhibition of PTR through a presynaptic effect; possible mechanisms are discussed. These observations may contribute to the understanding of the actions of this drug in epilepsy and neuromyotonia.

Volume 207, Issue 3, pp. 810-816, 12/01/1978
Copyright © 1978 by American Society for Pharmacology and Experimental Therapeutics