Elsevier

Biochemical Pharmacology

Volume 22, Issue 20, 15 October 1973, Pages 2615-2624
Biochemical Pharmacology

Inhibition of bovine brain aldehyde reductase by anticonvulsant compounds in vitro

https://doi.org/10.1016/0006-2952(73)90070-1Get rights and content

Abstract

The catalytic activity of partially purified NADPH-linked aldehyde reductase (alcohol: NADP oxidoreductase, EC 1.1.1.2) from bovine brain was markedly inhibited in vitro by anticonvulsant compounds. In general, the ability of these drugs to inhibit aldehyde reductase in vitro paralleled their anticonvulsant activity. Inhibition by various barbiturates, hydantoins or succinimides was non-competitive with either NADPH or aldehyde as the variable substrate, whereas the 2,4-oxazolidinediones produced a mixed type of inhibition. Inhibition by all ionizable compounds was found to vary with the pH of the reaction mixture, while the non-ionizable substances, paradione, trimethadione, methsuximide, 3-methyl-5-ethyl-5-phenylhydantoin, were not inhibitory. At pH 7.0 the inhibitor constants (Ki values) for phenobarbital, 5,5-diphenylhydantoin, 5,5-dimethyloxazolidinedione and ethosuximide were 1.2 × 10−4 M, 1.7 × 10−4 M, 4.7 × 10−4 M and 5.5 × 10−3 M respectively. The possibility that inhibition of brain NADPH-linked aldehyde reductase by these agents is concerned with their anticonvulsant actions is discussed.

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    This work was supported in part by Public Health Service Grants NIMH 18948, 18971 and 15908, National Institutes of Mental Health.

    Recipient of Career Development Award NIH.

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