Effects In-vitro of Procarbazine Metabolites on Some Amine Oxidase Activities in the Rat
| Autor: | Brian A. Callingham, Dennis F. Sharman, Andrew Holt |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Benzylamines
Amine oxidase Hydrochloride Monoamine oxidase Metabolite Deamination Pharmaceutical Science In Vitro Techniques Cofactor chemistry.chemical_compound Benzylamine Adipose Tissue Brown Monomethylhydrazine Animals Carbon Radioisotopes Pharmacology chemistry.chemical_classification Oxidoreductases Acting on CH-NH Group Donors biology Rats Enzyme Liver chemistry Biochemistry Procarbazine biology.protein Amine Oxidase (Copper-Containing) |
| Zdroj: | Journal of Pharmacy and Pharmacology. 44:494-499 |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1111/j.2042-7158.1992.tb03653.x |
| Popis: | The effects were examined of four metabolites of the anticancer agent, procarbazine (N-isopropyl-α-(2−methyl hydrazino)-p-toluamide hydrochloride) on semicarbazide-sensitive amine oxidase (SSAO) and monoamine oxidase-A and -B (MAO-A and -B) activities in rat brown adipose tissue and liver homogenates, respectively. Azoprocarbazine (AZO) and monomethylhydrazine (MMH) inhibited selectively the deamination of benzylamine by SSAO, when compared with their effects on MAO activities. The IC50 values against SSAO, of 32·7 Nm (AZO) and 7·0 Nm (MMH), were more than three orders of magnitude lower than those exhibited against MAO. Neither isomer of azoxyprocarbazine was an effective inhibitor of rat amine oxidase activities. The inhibition of SSAO by AZO was reversed very slowly by dialysis, in contrast to results seen for MMH. The non-competitive kinetics of MMH and the ability of B24, a rapidly reversible SSAO inhibitor, to protect SSAO against inhibition by MMH are consistent with the view that this compound binds to the enzyme cofactor at, or near, the active site. |
| Databáze: | OpenAIRE |
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