CHARACTERIZATION OF THE POTENTIAL ANTIOXIDANT AND PROOXIDANT ACTIONS OF SOME NEUROLEPTIC DRUGS

被引:97
作者
JEDING, I [1 ]
EVANS, PJ [1 ]
AKANMU, D [1 ]
DEXTER, D [1 ]
SPENCER, JD [1 ]
ARUOMA, OI [1 ]
JENNER, P [1 ]
HALLIWELL, B [1 ]
机构
[1] UNIV LONDON KINGS COLL,NEURODEGENERAT DIS RES CTR,PHARMACOL GRP,LONDON SW3 6LX,ENGLAND
关键词
NEUROLEPTICS; ANTIOXIDANT; FREE RADICAL; CHLORPROMAZINE; HEME PROTEINS; LIPID PEROXIDATION;
D O I
10.1016/0006-2952(94)00424-K
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
It has been suggested in the literature that neuroleptic drugs may be able to exert antioxidant and/or pro-oxidant actions in vivo. The feasibility of this was tested by measuring the ability of chlorpromazine, prochlorperazine, metoclopramide, methotrimeprazine and haloperidol to scavenge biologically relevant oxygen-derived species in vitro. None of the drugs reacted with superoxide radical at a significant rate. Chlorpromazine, prochlorperazine, metoclopramide and methotrimeprazine were very powerful scavengers of hydroxyl radicals, reacting at almost a diffusion-controlled rate. Chlorpromazine showed some ability to inhibit iron ion-dependent hydroxyl radical formation. Chlorpromazine, methotrimeprazine, promethazine and prochlorperazine were powerful inhibitors of iron ion-dependent liposomal lipid peroxidation, scavengers of organic peroxyl radicals and inhibitors of haem protein/hydrogen peroxide-dependent peroxidation of arachidonic acid. Chlorpromazine, prochlorperazine, metoclopramide, methotrimeprazine and haloperidol were powerful scavengers of hypochlorous acid. Haloperidol showed no ability to inhibit lipid peroxidation or to scavenge peroxyl radicals, and reproducibly increased lipid peroxidation catalysed by haem proteins, in both the presence and absence of hydrogen peroxide. The relevance of these in vitro observations to events in vivo is discussed.
引用
收藏
页码:359 / 365
页数:7
相关论文
共 45 条
[1]   EVALUATION OF THE ANTIOXIDANT AND PROOXIDANT ACTIONS OF GALLIC ACID AND ITS DERIVATIVES [J].
ARUOMA, OI ;
MURCIA, A ;
BUTLER, J ;
HALLIWELL, B .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 1993, 41 (11) :1880-1885
[2]   ANTIOXIDANT AND PROOXIDANT PROPERTIES OF ACTIVE ROSEMARY CONSTITUENTS - CARNOSOL AND CARNOSIC ACID [J].
ARUOMA, OI ;
HALLIWELL, B ;
AESCHBACH, R ;
LOLIGERS, J .
XENOBIOTICA, 1992, 22 (02) :257-268
[3]  
ARUOMA OI, 1989, XENOBIOTICA, V18, P459
[4]  
BECKMAN JS, 1991, J DIV PHYSL, V53, P53
[5]   NEUROLEPTIC-INDUCED SUPERSENSITIVITY AND BRAIN IRON .1. IRON-DEFICIENCY AND NEUROLEPTIC-INDUCED DOPAMINE-D2 RECEPTOR SUPERSENSITIVITY [J].
BENSHACHAR, D ;
YOUDIM, MBH .
JOURNAL OF NEUROCHEMISTRY, 1990, 54 (04) :1136-1141
[6]   ANTIOXIDANT ACTION AND PHOTOSENSITIZING EFFECTS OF 3 DIFFERENT CHLORPROMAZINES [J].
BINDOLI, A ;
RIGOBELLO, MP ;
FAVEL, A ;
GALZIGNA, L .
JOURNAL OF NEUROCHEMISTRY, 1988, 50 (01) :138-141
[7]   PHENOTHIAZINES INHIBIT COPPER AND ENDOTHELIAL CELL-INDUCED PEROXIDATION OF LOW-DENSITY-LIPOPROTEIN - A COMPARATIVE-STUDY WITH PROBUCOL, BUTYLATED HYDROXYTOLUENE AND VITAMIN-E [J].
BREUGNOT, C ;
MAZIERE, C ;
SALMON, S ;
AUCLAIR, M ;
SANTUS, R ;
MORLIERE, P ;
LENAERS, A ;
MAZIERE, JC .
BIOCHEMICAL PHARMACOLOGY, 1990, 40 (09) :1975-1980
[8]   REVERSAL OF AGE-RELATED INCREASE IN BRAIN PROTEIN OXIDATION, DECREASE IN ENZYME-ACTIVITY, AND LOSS IN TEMPORAL AND SPATIAL MEMORY BY CHRONIC ADMINISTRATION OF THE SPIN-TRAPPING COMPOUND N-TERT-BUTYL-ALPHA-PHENYLNITRONE [J].
CARNEY, JM ;
STARKEREED, PE ;
OLIVER, CN ;
LANDUM, RW ;
CHENG, MS ;
WU, JF ;
FLOYD, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (09) :3633-3636
[9]  
Cohen G, 1988, OXYGEN RADICALS TISS, P130
[10]   DETECTION OF MYOGLOBIN-DERIVED RADICALS ON REACTION OF METMYOGLOBIN WITH HYDROGEN-PEROXIDE AND OTHER PEROXIDIC COMPOUNDS [J].
DAVIES, MJ .
FREE RADICAL RESEARCH COMMUNICATIONS, 1990, 10 (06) :361-370