Inhibition of lipid hydroperoxidation of low density lipoprotein by the Ca(2+)-channel and alpha 1-adrenoceptor antagonist monatepil maleate.

The antioxidative effect of monatepil maleate (CAS 103379-03-9, AJ-2615), a new antihypertensive agent, was investigated by measuring its ability to inhibit copper-induced lipid hydroperoxidation of low density lipoprotein (LDL) and was compared with those of diltiazem (Ca 2+ -channel antagonist), prazosin (α 1 -adrenoceptor antagonist), and probucol. The concentration of AJ-2615 required to inhibit copper-induced lipid hydroperoxidation of LDL by 50 % (IC 50 ) was 28 μmol/l. The IC 50 values for diltiazem, prazosin, and probucol were > 1 mmol/l, > 1 mmol/l, and 17 μmol/l, respectively. These results indicate that AJ-2615 has the same potent antioxidative effect as probucol and suggest that a previously reported ability of AJ-2615 to inhibit the progression of atherosclerosis may be due to this antioxidative property. In addition, the dihydrodibenzothiepine ring of AJ-2615 may have an antioxidative function.