The use of aminopyridines in neurological disorders.
Aminopyridines are members of a family of monoamino and diamino derivatives of pyridine, and their principal mechanism of action is dose-dependent blockade of voltage-gated potassium channels, in particular, fast voltage-gated potassium channels. To date, only 2 main broad-spectrum potassium channel blockers, 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP), have been used as investigational new drugs in various neurological diseases. More recently, licensed versions of these compounds including dalfampridine extended release (Fampyra, Biogen Idec) for the improvement of walking in adult patients with multiple sclerosis, and amifampridine (Firdapse, Biomarin Europe Ltd) for the treatment of Lambert-Eaton myasthenic syndrome have been released, and the costs associated with using these new products highlights the importance of evaluating the clinically meaningful treatment effects of these drugs.The current review summarizes the evidence of aminopyridine use in neurological conditions and in particular presents a systematic review of all randomized trials of 3,4-DAP in Lambert-Eaton myasthenic syndrome to determine the efficacy of this treatment using meta-analysis of clinical and electrophysiological end points.
Department of Clinical Neurology, Queen's Medical Centre, Nottingham, UK. ssedehizadeh@doctors.org.uk
Saam
S
Sedehizadeh
Michael
M
Keogh
Paul
P
Maddison
D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077770:Amifampridine; D000631:Aminopyridines / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000188:drug therapy / Q000453:epidemiology; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000453:epidemiology; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods
D000631:Aminopyridines; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; D000077770:Amifampridine