Simvastatin inhibits the division and induces neurite-like outgrowth in PC12 cells.

Simvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. inhibited cell division in a dose dependent fashion and induced neurite-like outgrowth in PC12 cells. The neurite-like outgrowth was detectable at 0.5 microg/ml of simvastatin 24 h after the treatment. The responses to simvastatin were completely prevented by incubating the cells with mevalonate. In contrast to simvastatin, pravastatin, a similar HMG-CoA reductase inhibitor but lipophobic, had no effect on the cells. The results provide new possibilities for the central nervous system (CNS) side effects of simvastatin therapy.