Abstract
Chlorpromazine (CPZ), a major tranquilizer, was found to be a potent inhibitor of lecithin:cholesterol acyltransferase (LCAT, EC 2.3.1.43) in the plasma of normal man, rat, rabbit and dog in vitro. The inhibitory effect of CPZ reached 35-50% at 0.5 mM depending on species; dog plasma LCAT appeared to be somewhat more sensitive than that of the other species. In rats fed CPZ or lidocaine for 14 days (0.05% in the diet), there was no statistically significant change in total plasma cholesterol levels or the size of the plasma-free (unesterified) cholesterol pool. However, 5 hr after an intracardial injection of [14C]cholesterol, the percentage of plasma [14C]cholesterol that was esterified was significantly lower (ca. 6%, p less than 0.05) in the CPZ-treated group, suggesting that CPZ may also inhibit LCAT To some extent in vivo. The percentage of plasma [14C]cholesterol esterified in the lidocaine-treated group was similar to control values and did not reflect its ability to inhibit LCAT in vitro.
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