Linked Life Data

8415393

Source:http://linkedlifedata.com/resource/pubmed/id/8415393

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1993-11-18
pubmed:abstractText
The metabolism of racemic, (D)- and (L)-brompheniramine, a widely used antihistamine, was studied with microsomes and with highly purified flavin-containing monooxygenase (FMO) from hog liver. In addition, a number of other similar tertiary amines were evaluated as substrates for FMO activity from hog liver and the kinetic constants obtained were compared with brompheniramine. Although some N-demethylation was observed, the major metabolite of brompheniramine and the other tertiary amines examined in hog liver microsomes was the metabolite containing an aliphatic nitrogen N-oxide. Brompheniramine was extensively N-oxygenated by the highly purified FMO from hog liver. N-Oxygenation of brompheniramine in both microsomes and with highly purified FMO from hog liver was enantioselective. The Km for N-oxygenation of (D)-brompheniramine was markedly lower than the Km for (L)-brompheniramine. (E)- and (Z)-zimeldine are less conformationally flexible model compounds of brompheniramine, and these compounds were also examined and were found to be stereoselectively N-oxygenated by the highly purified FMO from hog liver. The similarities and differences in Km and Vmax values were evaluated in terms of possible conformations of the substrates determined by SYBYL molecular mechanics calculations. Distance map data indicated that FMO preferentially accommodated selected conformations of tertiary amines. Thus, (D)-brompheniramine and (Z)-zimeldine presumably have the aliphatic tertiary amine nitrogen atom and aromatic ring center at a defined distance and geometry and were more efficiently N-oxygenated than their respective isomers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0724-8741
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1097-105
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Tertiary amines related to brompheniramine: preferred conformations for N-oxygenation by the hog liver flavin-containing monooxygenase.
pubmed:affiliation
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't