Improvement in neuromuscular transmission in myasthenia gravis by 3,4-diaminopyridine

3,4-Diaminopyridine (3,4-DAP), a potent potentiator of action potential evoked release of acetylcholine from presynaptic terminals in the neuromuscular junction was given i.v. and p.o. to two patients with myasthenia gravis. Effects were monitored electrophysiologically by repetitive nerve stimulation and by standardized clinical testing. Administration of 8 mg and 9 mg 3,4-DAP i.v. produced a clear improvement in the neuromuscular transmission after approximately 20 min. When 3,4-DAP was given p.o. 24 mg was shown to be effective. At a dosage of 18-24 mg p.o. 3,4-DAP significantly potentiated the effect of the cholinesterase inhibitor pyridostigmine at an optimal dose. The maximal effect of 3,4-DAP p.o. was obtained after 2.5-3 h. No significant CNS side-effects were found which is in contrast to those reported for 4-aminopyridine. The results suggest that 3,4-DAP may be useful as an addition to the conventional treatment with cholinesterase inhibitors when immunosuppressive treatment is considered contraindicated or when it has not yet reached its full effect.