Presynaptic and postsynaptic actions of procainamide on neuromuscular transmission.
Procainamide (PA), a cardiac anti-arrhythmic agent, was applied in vitro to the rat neuromuscular junction and its effect on neuromuscular transmission was investigated using intracellular microelectrode recording techniques. Clinically relevant doses of PA produced a dose-dependent decrease in the amplitude of spontaneous miniature end-plate potentials (MEPPs) and a marked increase in the half-decay time without altering MEPP frequency or resting membrane potential. The amplitude of impulse-evoked end-plate potentials was also reduced in a similar dose-dependent manner, with a marked prolongation of the decaying phase. Direct quantal analysis using magnesium-blocked preparations showed that the drug also caused a reduction in the mean number of acetylcholine quanta released per nerve impulse. This presynaptic inhibitory effect of the drug, however, contributed less to the overall blocking action than did the postsynaptic effect. The junctional effects of the drug were completely reversible, with all affected parameters returning to the control levels after washout of PA with control solution. These direct inhibitory actions on neuromuscular transmission could account for the clinical exacerbations associated with the administration of PA to patients with myasthenia gravis and other neuromuscular diseases.
D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D011342:Procainamide / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D011342:Procainamide