Aminopyridines for the treatment of neurologic disorders
Strupp M, Teufel J, Zwergal A, Schniepp R, Khodakhah K, Feil K.
Neurol Clin Pract 2017; 7:65-76
Purpose of review:
To identify the different indications for the treatment of neurologic disorders with the potassium channel blockers 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP).
4-AP is an effective symptomatic treatment for downbeat nystagmus (DBN), episodic ataxia type 2 (EA2) (5–10 mg TID), and impaired gait in multiple sclerosis (MS) (10 mg BID). 3,4-DAP (5 mg/d–20 mg TID) improves symptoms in Lambert-Eaton myasthenic syndrome (LEMS) (randomized placebo-controlled trials for all 4 entities). 4-AP may also be effective in cerebellar gait ataxia of different etiologies (2 case series), upbeat nystagmus, and limb ataxia in MS (single cases). In the recommended dosages, they are well tolerated. The assumed mode of action is a blockade of mainly Kv1.5: in DBN, this increases the excitability of Purkinje cells (PC), and in EA2, restores the precision of resting discharge of PC. In MS, 4-AP improves the conduction of action potentials in demyelinated axons, and in LEMS, 3,4-DAP facilitates the transmission at the neuromuscular endplate by prolonging the action potential duration.
There is sufficient evidence that aminopyridines are indicated for the symptomatic treatment of downbeat nystagmus (DBN), episodic ataxia type 2 (EA2), gait ataxia due to MS and cerebellar disorders, and Lambert Eaton myasthenic syndrome (LEMS) with a reasonable risk-benefit profile.