Amantadine

Amantadine is an NMDA receptor antagonist with IC₅₀ values of 0.93, 0.82, and 0.47 μM at -70 mV for NR1-1a/NR2A, NR1-1a/NR2B, and NR1-1a/NR2D subunit-containing recombinant receptors, respectively, expressed in HEK293 cells.¹ It blocks the influenza A M2 proton channel (IC₅₀ = 16 μM for the recombinant channel expressed in Xenopus oocytes) and inhibits cytotoxicity induced by the influenza A strains H1N1 and H3N2 in MDCK cells (EC₅₀s = 34 and 0.84 μM, respectively).² It also improves the survival of mice infected with influenza A when administered 24 hours following viral challenge at a dose of 100 mg/kg per day.³ Amantadine (40 mg/kg) decreases dyskinesia induced by L-DOPA in a 6-OHDA hemi-parkinsonian mouse model.⁴ Formulations containing amantadine have been used in the treatment of various strains of influenza A virus infection and in the treatment of parkinsonism and drug-induced extrapyramidal symptoms.

1.Bresink, I., Benke, T.A., Collett, V.J., et al.Effects of memantine on recombinant rat NMDA receptors expressed in HEK 293 cellsBr. J. Pharmacol.119(2)195-204(1996) 2.Rey-Carrizo, M., Torres, E., Ma, C., et al.3-Azatetracyclo[5.2.1.15,8.01,5]undecane derivatives: From wild-type inhibitors of the M2 ion channel of influenza A virus to derivatives with potent activity against the V27A mutantJ. Med. Chem.56(22)9265-9274(2013) 3.Smee, D.F., Julander, J.G., Tarbet, E.B., et al.Treatment of oseltamivir-resistant influenza A (H1N1) virus infections in mice with antiviral agentsAntiviral Res.96(1)13-20(2012) 4.Bido, S., Marti, M., and Morari, M.Amantadine attenuates levodopa-induced dyskinesia in mice and rats preventing the accompanying rise in nigral GABA levelsJ. Neurochem.118(6)1043-1055(2011)