title: 3,4-diaminopyridine for the treatment of Lambert-Eaton myasthenic syndrome.
abstract: The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease in which antibodies against voltage-gated calcium channels inhibit cholinergic neurotransmission. LEMS is clinically characterized by muscle weakness and autonomic dysfunction. 3,4-diaminopyridine (3,4-DAP) blocks potassium channels in nerve terminals, resulting in an increase in acetylcholine release. This article describes the four randomized placebo-controlled trials of 3,4-DAP in patients with LEMS. All trials demonstrated a significant effect on muscle strength and compound muscle action potential amplitude. Furthermore, the safety and tolerability of 3,4-DAP are reviewed. The side effects of 3,4-DAP are generally mild and most frequently consist of paresthesias, but epileptic seizures and arrhythmias have been described in patients using high doses. Given the efficacy and safety of 3,4-DAP in LEMS, this drug is the mainstay for symptomatic treatment of LEMS.
authors.affiliation: Department of Neurology, Haga Hospital, The Hague, The Netherlands. p.wirtz@hagaziekenhuis.nl
authors.forename: Paul W
authors.initials: PW
authors.lastname: Wirtz
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Titulaer
authors.forename: Joop Ma van
authors.initials: JM
authors.lastname: Gerven
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Verschuuren
mesh_terms: D015761:4-Aminopyridine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000200:Action Potentials / Q000187:drug effects; D000077770:Amifampridine; D015220:Calcium Channels / Q000378:metabolism*; D018678:Cholinergic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002985:Clinical Protocols; D004827:Epilepsy / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000188:drug therapy* / Q000276:immunology; D009132:Muscles / Q000187:drug effects; D010292:Paresthesia / Q000209:etiology / Q000517:prevention & control; D017729:Presynaptic Terminals / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic
chemical_list: D015220:Calcium Channels; D018678:Cholinergic Agents; D015761:4-Aminopyridine; D000077770:Amifampridine