3,4-Diaminopyridine (amifampridine) for the treatment of Lambert–Eaton myasthenic syndrome

Abstract

Introduction: Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular junction resulting in muscle weakness and autonomic symptoms. LEMS often occurs as a paraneoplastic disease. Hallmarks of the disease are pathogenic antibodies against voltage-gated calcium channels, which cause a decrease in presynaptic acetylcholine release. 3,4-Diaminopyridine (3,4-DAP) is a potassium channel blocker, which leads to an increase of presynaptic calcium and improves the release of acetylcholine in LEMS patients.Areas covered: Here, the role of 3,4-DAP for the treatment of LEMS is reviewed. A literature search was carried out for the terms ‘3,4-diaminopyridine’ and ‘Lambert–Eaton myasthenic syndrome’. The information updates a previous review on the topic.Expert opinion: Small placebo-controlled studies have shown the efficacy of 3,4-DAP to treat muscle weakness in LEMS patients. A larger drug withdrawal study analyzing 30 patients on stable treatment with 3,4-DAP is under way. The efficacy of 3,4-DAP is moderate. There is a need to study the additional effects of pyridostigmine, a drug inhibiting acetylcholine breakdown used in myasthenia gravis, and the potential of novel calcium channel agonists. Apart from treating LEMS symptoms, 3,4-DAP may also be beneficial in the treatment of congenital myasthenic syndromes and myasthenia gravis caused by anti-muscle-specific kinase-antibodies.