Amifampridine, also known as Firdapse, is a presynaptic voltage-gated potassium channel blocker. This drug is used to treat Lambert-Eaton myasthenic syndrome. LEMS is an auto-immune disorder of the neuromuscular junction that is characterized by proximal muscle weakness, depressed tendon reflexes, and posttetanic potentiation in addition to autonomic dysfunction. This drug blocks presynaptic fast voltage-gated potassium channels, which prolongs the action potential and increases presynaptic calcium concentrations while increasing the acetylcholine concentrations at the neuromuscular junction. Increased intracellular calcium enhances the exocytosis of acetylcholine-containing vesicles and enhances impulse transmission at the synapses. It is administered as an oral tablet.
References
Amifampridine Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Lindquist S, Stangel M: Update on treatment options for Lambert-Eaton myasthenic syndrome: focus on use of amifampridine. Neuropsychiatr Dis Treat. 2011;7:341-9. doi: 10.2147/NDT.S10464. Epub 2011 May 30.
Oh SJ, Shcherbakova N, Kostera-Pruszczyk A, Alsharabati M, Dimachkie M, Blanco JM, Brannagan T, Lavrnic D, Shieh PB, Vial C, Meisel A, Komoly S, Schoser B, Sivakumar K, So Y: Amifampridine phosphate (Firdapse((R))) is effective and safe in a phase 3 clinical trial in LEMS. Muscle Nerve. 2016 May;53(5):717-25. doi: 10.1002/mus.25070. Epub 2016 Mar 3.
Ishida N, Kondo Y, Chikano Y, Kobayashi-Nakade E, Suga Y, Ishizaki J, Komai K, Matsushita R: Pharmacokinetics and tissue distribution of 3,4-diaminopyridine in rats. Biopharm Drug Dispos. 2019 Sep;40(8):294-301. doi: 10.1002/bdd.2203.
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