Inhibition of rat brain prostaglandin D synthase by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors

The effect of lovastatin, simvastatin and pravastatin, which are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was tested on PGD synthase purified to apparent homogeneity from the rat brain. Lovastatin and simvastatin, which reportedly cause insomnia in vivo, inhibited the PGD synthase activity dose-dependently and showed an IC50 value of 100 and 75 microM, respectively. On the other hand, pravastatin, which does not cause insomnia, showed no significant effect at 100 microM and only a slight effect up to 500 microM.