Citation

Holt A, Sharman DF, Callingham BA, Kettler R. J. Pharm. Pharmacol. 1992; 44(6): 487-493.

Copyright

(Copyright © 1992, Pharmaceutical Society of Great Britain)

DOI

10.1111/j.2042-7158.1992.tb03652.x

PMID

1359073

Abstract

Procarbazine (N-isopropyl-alpha-(2-methyl hydrazino)-p-toluamide hydrochloride) inhibited more powerfully the deamination of benzylamine by semicarbazide-sensitive amine oxidase (SSAO) of rat brown adipose tissue than the deamination of 5-hydroxytryptamine and benzylamine by rat liver monoamine oxidase-A or -B activities, respectively. Inhibition of SSAO, but not monoamine oxidase, was time-dependent. Use of metabolic inhibitors, and an enzyme dilution technique, suggested that any conversion of procarbazine to an active species must be as a result of the action of SSAO itself and not of any other enzyme. The non-competitive kinetics and the time-dependence of inhibition were indicative of a suicide interaction between procarbazine and SSAO. The slow reversal of inhibition by dialysis was evidence in favour of the involvement of tight binding, rather than covalent bonding. High concentrations of benzylamine afforded the enzyme significant protection from the action of procarbazine, indicating that the interaction is at or near the active site. If the properties of procarbazine, evident in in-vitro studies, are retained in-vivo, these data suggest that procarbazine might be suitable for the examination of SSAO activities, both in-vivo and ex-vivo.

Language: en

Keywords

Adipose Tissue, Brown; Amine Oxidase (Copper-Containing); Animals; Benzylamines; Carbon Radioisotopes; In Vitro Techniques; Liver; Oxidoreductases Acting on CH-NH Group Donors; Procarbazine; Rats