A Comparative Study on the Effects of Disulfiram, Cyanamide and 1‐Aminocyclopropanol on the Acetaldehyde Metabolism in Rats

Wiley - Tập 43 Số 3 - Trang 219-232 - 1978
Hans Marchner1, Olof Tottmar1
1From the Alcohol Research Group of the Swedish Medical Research Council, Institute of Zoophysiology, University of Uppsala, Box 560, S-751 22 Uppsala, Sweden

Tóm tắt

Abstract 1‐aminocyclopropanol (ACP) is a potent inhibitor of aldehyde dehydrogenase (ALDH) in vivo and in vitro. Like cyanamide it has a rapid onset of action in vivo with the highest inhibition occurring after 2‐24 hrs. and a long duration of action like disulfiram with measurable inhibition after 144 hrs. All the three inhibitors decreased the activity of the mitochondrial low‐Km ALDH strongly in vivo, however, in markedly different doses. Cyanamide inhibited the high‐Km ALDH only in vivo, whereas in vitro, the high‐Km ALDH was unaffected by cyanamide but significantly inhibited by disulfiram and ACP. The inhibition produced by the inhibitors appeared to be irreversible. Acetaldehyde protected the low‐Km enzyme at different extents depending on the inhibitor used. The inhibition of ALDH in intoxicated and control rats and its relation to acetaldehyde oxidation and the disulfiram‐ethanol reaction are discussed.

Từ khóa


Tài liệu tham khảo

10.1016/0041-008X(65)90084-0

10.1177/16.10.611

10.1111/j.1749-6632.1964.tb14213.x

Deitrich R.A., 1963, Diphosphopyridine nucleotide‐linked aldehyde dehydrogenase. II. Inhibitors, J. Biol. Chem., 238, 1683, 10.1016/S0021-9258(18)81121-8

Deitrich R.A., 1971, Mechanism of the inhibition of aldehyde dehydrogenase in vivo by disulfiram and diethyldithiocarbamate, Mol. Pharmacol., 7, 301

Deitrich R.A., 1974, Alcohol and aldehyde metabolizing systems., 125

10.1016/0006-2952(76)90265-3

Ferguson J.K.W., 1956, A new drug for alcoholism treatment, Can. Med. Ass. J., 74, 793

10.1042/bj0970587

Hald J., 1948, The formation of acetaldehyde in the organism after ingestion of antabuse (tetraethylthiuramdisulphide) and alcohol, Acta pharmacol. et toxicol., 4, 286, 10.1111/j.1600-0773.1948.tb03352.x

Hatfield G.M., 1975, Isolation and structural studies of Coprine, the disulfiram‐like constituent of Coprinus atramentarius, Lloydia., 38, 489

10.1042/bj1510407

10.15288/jsa.1977.38.96

10.1016/0006-2952(75)90250-6

10.1042/bj1120117

10.1177/070674377502000406

10.1039/c39750000946

Lindros K.O., 1975, The role of acetaldehyde in the actions of ethanol, 67

10.1192/bjp.125.5.485

10.1111/j.1600-0773.1976.tb03099.x

10.1111/j.1600-0773.1976.tb03184.x

10.1016/0005-2744(73)90406-3

10.1016/0006-2952(69)90150-6

10.1111/j.1360-0443.1974.tb01317.x

10.1042/bj1350577a

Tottmar S.O.C., 1974, Alcohol and aldehyde metabolizing systems., 147

10.1111/j.1600-0773.1976.tb03132.x

10.1111/j.1600-0773.1977.tb02100.x

10.1007/978-1-4615-6525-3_5

Wallgren H., 1970, Actions of alcohol., 43

Thông tin
Thông tin xuất bản

Wiley

Tập 43 Số 3

219-232

Thông tin tác giả