The metabolism of propranolol and oxprenolol will be investigated. Stereochemical aspects of the aromatic hydroxylation processes will be investigated in vivo and in vivo in rodents. Structure determination of the phenolic metabolites produced will be investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM025373-06
Application #
3272968
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1978-12-01
Project End
1986-11-30
Budget Start
1985-04-01
Budget End
1986-11-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Pharmacy
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Dumas, J J; Zhu, Z; Connolly, J L et al. (1999) Structural basis of activation and GTP hydrolysis in Rab proteins. Structure 7:413-23
Piknova, B; Marsh, D; Thompson, T E (1996) Fluorescence-quenching study of percolation and compartmentalization in two-phase lipid bilayers. Biophys J 71:892-7
Murthy, S S; Nelson, W L; Shen, D D et al. (1991) Pharmacokinetic interaction between verapamil and metoprolol in the dog. Stereochemical aspects. Drug Metab Dispos 19:1093-100
Weerawarna, S A; Geisshusler, S M; Murthy, S S et al. (1991) Enantioselective and diastereoselective hydroxylation of bufuralol. Absolute configuration of the 7-(1-hydroxyethyl)-2-[1-hydroxy-2-(tert-butylamino)ethyl]benzofurans, the benzylic hydroxylation metabolites. J Med Chem 34:3091-7
Murthy, S S; Shetty, H U; Nelson, W L et al. (1990) Enantioselective and diastereoselective aspects of the oxidative metabolism of metoprolol. Biochem Pharmacol 40:1637-44
Shetty, H U; Nelson, W L (1988) Chemical aspects of metoprolol metabolism. Asymmetric synthesis and absolute configuration of the 3-[4-(1-hydroxy-2-methoxyethyl)phenoxy]-1-(isopropylamino)-2-propanols , the diastereomeric benzylic hydroxylation metabolites. J Med Chem 31:55-9
Gustavson, L M; Nelson, W L (1988) Regioisomeric products of propranolol metabolism. The monomethyl ethers of 3,4-dihydroxypropranolol and of 3,4-dihydroxypropranolol glycol. Drug Metab Dispos 16:217-21
Talaat, R E; Nelson, W L (1988) Regioisomeric aromatic dihydroxylation of propranolol. Use of monohydroxylated intermediates for structural assignments of the metabolites formed in vitro. Drug Metab Dispos 16:207-11
Talaat, R E; Nelson, W L (1988) Regioisomeric aromatic dihydroxylation of propranolol. Synthesis and identification of 4,6- and 4,8-dihydroxypropranolol as metabolites in the rat and in man. Drug Metab Dispos 16:212-6
Shetty, H U; Nelson, W L (1986) Chemical and stereochemical aspects of propranolol metabolism. Diastereomeric 1-(1-hydroxy-2-propylamino)-3-(1-naphthoxy)-2-propanols produced by rat liver microsomal omega-hydroxylation. J Med Chem 29:2004-8

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