Amantadine and tromantadine are agents used against influenza and herpes infections, respectively. Tromantadine raises the bilayer to hexagonal phase transition temperature of synthetic phosphatidylethanolamines and is less disruptive to phospholipid packing. Tromantadine acts similar to cyclosporin A, previously demonstrated to inhibit viral-induced cell-cell fusion. We suggest the balance between the hydrophobic and hydrophilic group sizes would allow tromantadine to prevent membrane fusion more than amantadine and thus inhibit infection by viruses such as Herpes, which fuse with the plasma membrane. Study of agents which stabilize the bilayer phase of membranes may lead to efficacious inhibitors of viral infections requiring cell fusion events.
Abbreviations DEPE, dielaidoyl phosphatidylethanolamine; POPE, 1-palmitoyl-2-oleoyl phosphatidylethanolamine; DMPC, dimyristoyl phosphatidylcholine; DSC, differential scanning calorimetry; PIPES, piperazine-N,N′-bis(2-ethanesulphonic acid); NMR, nuclear magnetic resonance; tromantadine, N-1-adamantyl-N-[2-(dimethylamino)ethoxy]a(ethoxy]acetamide-hydrochloride; amantadine, (1-adamantamine)-hydrochloride; HSV, Herpes Simplex Virus