Terbinafine inhibits the mitogenic response to platelet-derived growth factor in vitro and neointimal proliferation in vivo.

Terbinafine [(E)-N(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthale nemethanamine], an antimycotic agent that inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated aortic smooth muscle cell DNA synthesis in vitro and neointimal proliferation in vivo. Exposure of bovine aortic smooth muscle cells to 0.25 to 25 microM terbinafine resulted in a concentration-dependent inhibition of PDGF-induced mitogenesis as determined by [3H]thymidine incorporation into DNA or cell number. The IC50 for inhibition of PDGF-stimulated smooth muscle cell DNA synthesis was approximately 5 microM. Micromolar concentrations of terbinafine also suppressed the mitogenic response to PDGF in fibroblasts. Neither the binding of [125I]PDGF to its plasma membrane receptors nor the uptake of [3H]thymidine or [3H]uridine was affected significantly by terbinafine. Oral administration of terbinafine (200 mg/kg/day) to rats for 2 days before and 14 days after balloon catheter injury to the carotid artery was associated with a 40% decrease in the area of the neointimal lesion. These observations indicate that terbinafine is both a potent in vitro antagonist of the smooth muscle cell mitogenic response to PDGF and an effective, well-tolerated p.o. active inhibitor of neointimal proliferation in vivo.