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 (alpha 1-adrenoceptor antagonist), and probucol. The concentration of AJ-2615 required to inhibit copper-induced lipid hydroperoxidation of LDL by 50% (IC50) was 28 mumol/l. The IC50 values for diltiazem, prazosin, and probucol were > 1 mmol/l, > 1 mmol/l, and 17 mumol/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 functions.
Hayashi
K
K
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Kuga
Y
Y
Nomura
S
S
Okura
Y
Y
Tanaka
K
K
Yasunobu
Y
Y
Nomura
K
K
Shingu
T
T
Kuwashima
J
J
Kajiyama
G
G
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry; D019327:Copper Sulfate; D003864:Depression, Chemical; D003988:Dibenzothiepins / Q000737:chemistry / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011341:Probucol / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000924:Anticholesteremic Agents; D002121:Calcium Channel Blockers; D003988:Dibenzothiepins; D008077:Lipoproteins, LDL; D010879:Piperazines; D003300:Copper; D004110:Diltiazem; D019327:Copper Sulfate; C067818:monatepil; D011341:Probucol; D011224:Prazosin