Differential effects of the anticonvulsants phenobarbital, ethosuximide and carbamazepine on neuromuscular transmission.
The actions of the anticonvulsants phenobarbital, ethosuximide and carbamazepine were examined electrophysiologically at the frog neuromuscular junction. Phenobarbital reduced miniature end-plate potential (MEPP) amplitude, did not significantly affect end-plate potential amplitude and increased quantal content. Ethosuximide decreased MEPP and end-plate potential amplitudes proportionally; quantal content was unchanged. Carbamazepine decreased end-plate potential amplitude more than MEPP amplitude; quantal content was decreased. In a solution containing elevated (7.5 mM) K+, phenobarbital and carbamazepine increased MEPP frequency, whereas ethosuximide had no effect. Carbamazepine had to be dissolved in a solvent, propylene glycol, which was shown to produce small, but sometimes statistically significant, alterations in the measured parameters of neuromuscular transmission. The results show that all three of these anticonvulsants depress postjunctional sensitivity to released acetylcholine producing parallel dose-response curves for MEPP amplitude inhibition. These experiments also show that these drugs exhibit different mechanisms of action with respect to nerve-stimulated neurotransmitter release from nerve terminals at the neuromuscular junction: phenobarbital enhances acetylcholine release, ethosuximide has no effect and carbamazepine decreases transmitter release.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002220:Carbamazepine / Q000494:pharmacology*; D005013:Ethosuximide / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009469:Neuromuscular Junction / Q000502:physiology; D010634:Phenobarbital / Q000494:pharmacology*; D011894:Rana pipiens; D009435:Synaptic Transmission / Q000187:drug effects*
D002220:Carbamazepine; D005013:Ethosuximide; D000109:Acetylcholine; D010634:Phenobarbital