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Tuesday, 26 January 2010

2010 New Drug Approvals - Pt. II - Dalfampridine (Ampyra)


The second NME approval this year is Dalfampridine (trade name Ampyra), approved on January 22nd. Dalfampridine is a potassium channel blocker indicated to improve walking in adults with multiple sclerosis. Multiple sclerosis is a serious chronic disease that affects the central nervous system and in which the myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring. The therapeutic mechanism of Dalfampridine is complex, has not been fully elucidated, but it has been shown to increase conduction of action potentials in demyelinated axons through inhibition of potassium channels, probably Shaker channels.

Dalfampridine is a (very) small molecule drug (Molecular Weight 94.1 g.mol-1), fully Rule-of-Five compliant and soluble in water. Dalfampridine (also known as 4-AP) has good oral bioavailability (96% bioavailable), with a volume of distribution of 2.6 L/kg and low plasma protein binding. Excretion is mainly renal (95.9% of the dose recovered in urine) and mostly as the parent drug (90.3%). Dalfampridine metabolites are 3-hydroxy-4-aminopyridine and 3-hydroxy-4-aminopyridine sulfate (a sulphated form of the previous metabolite). These metabolites have no pharmacological activity on potassium channels. The elimination half-life of Dalfampridine is 5.2-6.5 hours. The maximum recommended dosage is 10mg twice daily (equivalent to a dose of 106uM) and full prescribing information can be found here. Dalfampridine chemical structure is 4-aminopyridine, a very simple unremarkable structure.

NAME="Dalfampridine" TRADEMARK_NAME="Ampyra"
SMILES="n1ccc(N)cc1"
InChI="InChI=1/C5H6N2/c6-5-1-3-7-4-2-5/h1-4H,(H2,6,7)"
InChIKey="NUKYPUAOHBNCPY-UHFFFAOYAH"
ChemDraw=Dalfampridine.cdx

The license holder is Acorda Therapeutics, Inc. and the product website is www.ampyra.com.

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