Formation of a direct mutagen, diazo-N-nitrosoetilefrin, by interaction with nitrite

• 菊川 清見

  Tokyo College of Pharmacy

• 加藤 哲太

  Tokyo College of Pharmacy

• 武田 寧

  National Institute of Hygienic Sciences

抄録

Reaction of an antihypotensive drug, etilefrin [α-{(ethylamino)methyl}-m-hydroxybenzyl alcohol], with nitrite under mildly acidic conditions produced N-nitrosoetilefrin [α-{(N-nitrosoethylamino)methyl}-m-hydroxybenzyl alcohol] (a mixture of syn and anti forms) (Iab) and diazo-N-nitrosoetilefrin [1-(4-diazo-3-oxo-1,5-cyclohexadienyl-2-(N-nitrosoethylamino)ethanol] (a mixture of syn and anti forms) (IIab). Treatment of etilefrin with an equivalent amount of nitrite at pH 3 and 37℃ for 4 h gave lab (yield, 30%) and IIab (yield, 5%). Treatment of eilefrin with 4 eq of nitrite under the same conditions gave Iab (23%) and IIab (53%). Compounds Iab IIab were each composed of two isomers due to the configuration of the N-nitroso group. While compound Iab was not mutagenic, compound IIab showed mutagenicity to Salmonella typhimurium TA98 and TA100 strains without metabolic activation. Specific mutagenic activity of IIab was 300 his^+ revertant colonies for both TA98 and TA100 strains with a dose of 0.1μmol. Addition of a microsomal activation system little affected the activity. It is noteworthy that this orally administered drug can produce a direct-acting mutagen by reaction with nitrite, which is present in the digestive tract.

収録刊行物

• Chem. Pharm. Bull.

  Chem. Pharm. Bull. 37 1600-1603, 1989

  公益社団法人日本薬学会

キーワード

• etilefrin
• N-nitrosoetilefrin
• diazo-N-nitrosoetilefrin
• mutagenicity

詳細情報

• CRID: 1571980077391622016
• NII論文ID: 110003627811
• NII書誌ID: AA00602100
• ISSN: 00092363
• 本文言語コード: en
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