{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:52:22Z","timestamp":1782993142734,"version":"3.54.5"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> 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.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> to assess 3,4-diaminopyridine (3,4-DAP) effects and tolerability in patients with anti-AChR myasthenia gravis.<\/jats:p><jats:p><jats:bold>Method:<\/jats:bold> 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\u00a0mg per os in 15 patients. Patients were divided according to their Myasthenia Gravis Foundation of America (MGFA) class into mild and severe.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> No significant side effects were found, apart from transient paresthesia. 3,4-DAP had a significant effect on the QMG score (<jats:italic>p<\/jats:italic> = 0.0251), on repetitive nerve stimulation (<jats:italic>p<\/jats:italic> = 0.0251), and on the forced vital capacity (<jats:italic>p<\/jats:italic> = 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 <jats:italic>severe<\/jats:italic> group, either for the QMG score (<jats:italic>p<\/jats:italic> = 0.031) or for the RNS decrement (<jats:italic>p<\/jats:italic> = 0.031). No significant difference was observed in any of the outcome measures within the <jats:italic>mild<\/jats:italic> group (<jats:italic>p<\/jats:italic> &amp;gt; 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.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> 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.<\/jats:p>","DOI":"10.3389\/fphar.2022.982434","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T06:57:35Z","timestamp":1660633055000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of 3,4-diaminopyridine on myasthenia gravis: Preliminary results of an open-label study"],"prefix":"10.3389","volume":"13","author":[{"given":"Marco","family":"Ceccanti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Libonati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Ruffolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierangelo","family":"Cifelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Moret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Frasca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Inghilleri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cambieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1212\/01.WNL.0000163988.28892.79","article-title":"Quantitative Myasthenia Gravis Score: Assessment of Responsiveness and Longitudinal Validity","volume":"64","author":"Bedlack","year":"2005","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2050312118819013","DOI":"10.1177\/2050312118819013","article-title":"Amifampridine Phosphate in the Treatment of Muscle-specific Kinase Myasthenia Gravis: a Phase IIb, Randomized, Double-Blind, Placebo-Controlled, Double Crossover Study","volume":"6","author":"Bonanno","year":"2018","journal-title":"SAGE Open Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.taap.2018.01.012","article-title":"3, 4-diaminopyridine Reverses Paralysis in Botulinum Neurotoxin-Intoxicated Diaphragms through Two Functionally Distinct Mechanisms","volume":"341","author":"Bradford","year":"2018","journal-title":"Toxicol. 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