TROMANTADINE

Tromantadine inhibits herpes simplex virus type 1 (KOS strain)-induced cytopathic effect and virus replication with limited toxicity to the cells. Vero and HEp-2 cells tolerate up to 2 mg of Tromantadine per 2x10 ⁶ cells for 24-, 48-, or 96-h incubation periods with little change in cell morphology. Treatment of the cells with 10 to 50 μg of Tromantadine reduces herpes simplex virus-induced cytopathic effect. Treatment with 100 to 500 μg of Tromantadine inhibits herpes simplex virus-induced cytopathic effect and reduces virus production. Complete inhibition of virus production is observed with treatments of 500 μg to 1 mg. The antiherpetic activity of Tromantadine is dependent upon the viral inoculum size and the time of addition of the compound with respect to infection. Virion synthesis and viral polypeptide synthesis are inhibited by addition of Tromantadine at the time of infection or 4 h postinfection. 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.