10476-53-6Relevant articles and documents
Covalent binding of a reactive metabolite derived from propranolol and its active metabolite 4-hydroxypropranolol to hepatic microsomal proteins of the rat
Narimatsu, Shizuo,Arai, Takayuki,Watanabe, Toshiyuki,Masubuchi, Yasuhiro,Horie, Toshiharu,Suzuki, Tokuji,Ishikawa, Tsutomu,Tsutsui, Michio,Kumagai, Yoshito,Cho, Arthur K.
, p. 289 - 295 (1997)
Repeated administration of propranolol (PL) to rats causes the inhibition of cytochrome P450-2D (P450-2D) enzyme. We recently found that 4- hydroxypropranolol (4-OH-PL) was biotransformed to 1,4-naphthoquinone (1,4- NQ) by superoxide (SO) anions in medium containing rat liver microsomes and NADPH and proposed that the binding of the quinone to P450-2D apoproteins might be one of mechanisms for the enzyme inhibition [Narimatsu et al. (1995) Chem. Res. Toxicol. 8, 721-728]. In this study, we have searched for possible sources of SO for the conversion of 4-OH-PL to 1,4-NQ in rat liver microsomes and determined the radioactivity covalently bound to microsomal proteins after incubation of radioactive PL and 4-OH-PL with rat liver microsomes. Elimination of 4-OH-PL from a mixture containing microsomes and NADPH was suppressed by carbon monoxide. Antibodies raised to P450-2B1 and -3A2 partially, and antibody against NADPH-cytochrome P450 reductase (fp2) markedly suppressed the reaction. 1,4-NQ was formed concomitantly with 4-OH- PL elimination by a reconstituted preparation of fp2. Binding studies using naphthalene ring (NR)- and side chain (SC)-radiolabeled PL and 4-OH-PL showed that radioactivity covalently bound to microsomal proteins was much higher from 4-OH-PL than from PL for the NR-labeled compounds, but higher from PL than from 4-OH-PL for the SC-labeled compounds. These results suggest that the 4-OH-PL formed from PL by P450-2D enzyme is converted to 1,4-NQ with loss of the side chain, and the 1,4-NQ accounts for most of the radioactivity covalently bound to microsomal proteins, including the P450-2D enzymes. The SO for conversion of 4-OH-PL to 1,4-NQ is supplied mainly by fp2 with some contribution by P450 enzymes.
Multistage Reactive Transmission-Mode Desorption Electrospray Ionization Mass Spectrometry
Peters, Kevin C.,Comi, Troy J.,Perry, Richard H.
, p. 1494 - 1501 (2015/08/18)
Elucidating reaction mechanisms is important for advancing many areas of science such as catalyst development. It is often difficult to probe fast reactions at ambient conditions with high temporal resolution. In addition, systems involving reagents that
Ring-hydroxylated propranolol: Synthesis and β-receptor antagonist and vasodilating activities of the seven isomers
Oatis Jr.,Russell,Knapp,Walle
, p. 309 - 314 (2007/10/02)
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