Effects of 3,4-diaminopyridine on myasthenia gravis: Preliminary results of an open-label study.

3,4-diaminopyridine (3,4-DAP) can lead to clinical and electrophysiological improvement in myasthenic syndrome; it may thus represent a valuable therapeutic option for patients intolerant to pyridostigmine. to assess 3,4-diaminopyridine (3,4-DAP) effects and tolerability in patients with anti-AChR myasthenia gravis. Effects were monitored electrophysiologically by repetitive nerve stimulation (RNS) and by standardized clinical testing (QMG score) before and after a single dose administration of 3,4-DAP 10 mg per os in 15 patients. Patients were divided according to their Myasthenia Gravis Foundation of America (MGFA) class into mild and severe. No significant side effects were found, apart from transient paresthesia. 3,4-DAP had a significant effect on the QMG score ( = 0.0251), on repetitive nerve stimulation ( = 0.0251), and on the forced vital capacity ( = 0.03), thus indicating that it may reduce the level of disability and the decremental muscle response. When the patients were divided according to the MGFA classification, 3,4-DAP showed a positive effect in the group, either for the QMG score ( = 0.031) or for the RNS decrement ( = 0.031). No significant difference was observed in any of the outcome measures within the group ( > 0.05). A direct effect of 3,4-DAP on nicotinic ACh receptors (nAChRs) was excluded since human nAChRs reconstituted in an expression system, which were not affected by 3,4-DAP application. Our results suggest that 3,4-DAP may be a useful add-on therapy, especially in most severe patients or when immunosuppressive treatment has not yet reached its full effect or when significant side-effects are associated with anticholinesterase.