4-Aminopyridine (4-AP, fampridine, dalfampridine) is an organic compound with the chemical formula C5H4N–NH2. The molecule is one of the three isomeric amines of pyridine. It is used as a research tool in characterizing subtypes of the potassium channel. It has also been used as a drug, to manage some of the symptoms of multiple sclerosis, and is indicated for symptomatic improvement of walking in adults with several variations of the disease. It was undergoing Phase III clinical trials as of 2008, and the U.S. Food and Drug Administration (FDA) approved the compound on January 22, 2010. Fampridine is also marketed as Ampyra (pronounced "am-PEER-ah," according to the makers website) in the United States by Acorda Therapeutics and as Fampyra in the European Union, Canada, and Australia. In Canada, the medication has been approved for use by Health Canada since February 10, 2012. Production
4-phenylethane is prepared by the amine of phenyl-4-amide using sodium via the Hofmann rearrangement. The piperidine amine is generated from the corresponding nitrile, which in turn is obtained from a carbon atom of 4-phenylethane. Applications
In the laboratory, 4-AP is a useful pharmacological tool in studying various potassium conductances in physiology and biophysics. It is a relatively selective blocker of members of Kv1 (Shaker, KCNA) family of voltage-activated K+ channels. However, 4-AP has been shown to potentiate voltage-gated Ca2+ channel currents independent of effects on voltage-activated K+ channels. Convulsant activity
4-Aminopyridine is a potent convulsant and is used to generate seizures in animal models for the evaluation of antiseizure agents.
4-AP should not be given to people with significant kidney disease (e.g., acute kidney injury or advanced chronic kidney disease) due to the higher risk of seizures with increased circulating levels of 4-AP. Branding
The drug was originally intended, by Acorda Therapeutics, to have the brand name Amaya, however the name was changed to Ampyra to avoid potential confusion with other marketed pharmaceuticals.Four of Acordas patents pertaining to Ampyra were invalidated in 2017 by the United States District Court for the District of Delaware and a fifth patent expired in 2018. Since then, generic alternatives have been developed for the U.S. market.The drug is marketed by Biogen Idec in Canada as Fampyra and as Dalstep in India by Sun Pharma. Research
Parkinsons disease
Dalfampridine completed Phase II clinical trials for Parkinsons disease in July 2014. See also
4-Dimethylaminopyridine, a popular laboratory reagent, is prepared directly from pyridine instead of via methylating this compound. Pyridine
4-Pyridylnicotinamide, useful as a ligand in coordination chemistry, is prepared by the reaction of this compound with nicotinoyl chloride. References
External links
"Dalfampridine". Drug Information Portal. U.S. National Library of Medicine.