Inhibition of Cholesterol Synthesis in vivo by a Convulsant,Metrazol. ∗

Summary

Pentamethylene tetrazol inhibited the incorporation of acetate-1-C¹⁴ into sterols in intact mice even after a single injection. Prolonged treatment of mice with very low, subconvulsive, doses of the drug resulted in a 20% decrease in plasma cholesterol level, as well as a pronounced decrease in the amount of radioactivity found in liver sterols synthesized from acetate-1-C¹⁴ or mevalonate-2-C¹⁴ but not from squalene-C¹⁴ or lanosterol-T. Metrazol treatment also resulted in almost complete absence of radioactivity in carbon dioxide exhaled by treated animals injected with mevalonate-2-C¹⁴. These findings indicate that the site of action of Metrazol along the acetate-cholesterol pathway lies between mevalonate and squalene.