By Marcello Cherchi, MD PhD
For patients
There are a few aminopyridine medications. Sometimes these drugs are used to help patients who find it difficult to see or walk because of a problem in the part of the brain called the cerebellum.
For clinicians
Overview
Aminopyridines are potassium channel blockers that prolong a neuron’s action potential. In otoneurology these drugs are sometimes used in the management of cerebellar disorders.
Introduction
Several aminopyridines are available:
- 4‑aminopyridine (dalfampridine, currently marketed in the US as Ampyra®)
- 4‑aminopyridine, extended release (fampridine) (Muth et al. 2021)
- 3,4‑diaminopyridine (not currently FDA-approved)
Pharmacology
Aminopyridines are broad-spectrum voltage-dependent potassium channel blockers (Lugaresi 2015) that influence the depolarizing potential in axonal membranes, thereby prolonging the action potential. These drugs were originally developed for the treatment of gait disorders associated with multiple sclerosis based on the idea that prolongation of an action potential might offset the impaired conduction from demyelination (Egeberg et al. 2012).
Comparing “3,4‑diaminopyridine and 4-aminopyridine; the latter penetrates the blood-brain barrier better, has a longer half-life, and is generally better tolerated” (Leigh and Rucker 2005).
Relevance in otoneurology
Sites of action relevant to otoneurology include Purkinje cells in the cerebellar cortex. Aminopyridines have been applied in the management of spontaneous down beat nystagmus due to a variety of disorders, including Chiari malformation type 1, and episodic ataxia type 2. There has been a placebo-controlled study of 3,4‑diaminopyridine (Strupp et al. 2003) and a crossover study of 4‑aminopyridine and 3,4‑diaminopyridine (Polman et al. 1994).
In the United States the drug 4‑aminopyridine, also called dalfampridine, is FDA approved, whereas 3,4‑diaminopyridine is not and must be obtained through compounding pharmacies.
References
Egeberg MD, Oh CY, Bainbridge JL (2012) Clinical overview of dalfampridine: an agent with a novel mechanism of action to help with gait disturbances. Clin Ther 34: 2185-94. doi: 10.1016/j.clinthera.2012.10.003
Leigh JR, Rucker JC (2005) Nystagmus and related ocular motility disorders. In: Miller NR, Newman NJ (eds) Walsh & Hoyt’s Clinical Neuro-Ophthalmology, 6th edition edn, vol 1. Lippincott Williams & Wilkins, 530 Walnut Street, Philadelphia, Pennsylvania 19106 USA; 351 West Camden Street, Baltimore, Maryland 21201-2436 USA, pp 1133-1173
Lugaresi A (2015) Pharmacology and clinical efficacy of dalfampridine for treating multiple sclerosis. Expert Opin Drug Metab Toxicol 11: 295-306. doi: 10.1517/17425255.2015.993315
Muth C, Teufel J, Schols L, Synofzik M, Franke C, Timmann D, Mansmann U, Strupp M (2021) Fampridine and Acetazolamide in EA2 and Related Familial EA: A Prospective Randomized Placebo-Controlled Trial. Neurol Clin Pract 11: e438-e446. doi: 10.1212/CPJ.0000000000001017
Polman CH, Bertelsmann FW, de Waal R, van Diemen HA, Uitdehaag BM, van Loenen AC, Koetsier JC (1994) 4-Aminopyridine is superior to 3,4-diaminopyridine in the treatment of patients with multiple sclerosis. Arch Neurol 51: 1136-9. doi: 10.1001/archneur.1994.00540230074016
Strupp M, Schuler O, Krafczyk S, Jahn K, Schautzer F, Buttner U, Brandt T (2003) Treatment of downbeat nystagmus with 3,4-diaminopyridine: a placebo-controlled study. Neurology 61: 165-70. doi: 10.1212/01.wnl.0000078893.41040.56
