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Title: Evidence that chlorpromazine inhibits sterologenesis at post-HMGCoA reductase sites in rat liver, in vitro. Author: Bell FP, Hubert EV. Journal: Lipids; 1983 Sep; 18(9):668-71. PubMed ID: 6633175. Abstract: The mechanism by which chlorpromazine inhibits cholesterogenesis in rat liver was investigated in vitro with the use of [14C] acetate and [14C] mevalonate as sterol precursors. Evidence was obtained that chlorpromazine blocks cholesterogenesis at multiple sites beyond HMGCoA reductase (beta-hydroxy-beta-methylglutarylCoA reductase, EC 1.1.1.34), the rate-limiting step. Squalene synthesis from both labeled acetate and mevalonate is reduced to a similar extent in the presence of chlorpromazine (29-36% at 0.5 mM). The data indicate that there is also an impairment of conversion of squalene to lanosterol, and of lanosterol to cholesterol. Overall inhibition of cholesterogenesis by chlorpromazine reached 65-75% at 0.5 mM and was concentration-dependent over the range 0.15-1.0 mM.[Abstract] [Full Text] [Related] [New Search]