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| School of Pharmacy > Department of Medicinal Chemistry > Faculty, Wendel L. Nelson | ||
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ACADEMIC BIO 
RESEARCH OVERVIEW Research activities are concerned with chemical aspects of drug metabolism and drug action from mechanistic and stereochemical viewpoints. Many drugs are used as racemic mixtures in which the optical isomers (enantiomers) have different pharmacological or toxicological properties, as well as different rates or pathways of metabolism. We are particularly interested in exploring pathways of the metabolism of cardiovascular drugs, agents widely used for the treatment of hypertension and other diseases. Among these are the β-adrenergic blocking agents and calcium channel antagonists. We have prepared enantiomers labeled specifically with deuterium or 13C, and we are studying the metabolism of the compounds as pseudoracemates (equimolar mixtures of the enantiomers in which only one of the enantiomers is labeled). A number of putative metabolites are synthesized to confirm their identity. Expected intermediates in metabolic processes and diastereomeric metabolites of known stereochemistry are synthesized, identified and quantitated. In this way, we can examine the metabolic pathways for their formation to obtain an understanding of how the drugs are metabolized. Ongoing work with others includes the synthesis and purification of metabolites and potential metabolic intermediates for studies related to the formation of metabolic inhibitor complexes that occur in the metabolism of secondary and tertiary amine drugs, e.g., synthesis of hydroxylamines, nitrones, and nitroso compounds. Among the drugs under study are imipramine, fluoxetine, and fluvoxamine, tamoxifen, and diltiazem. Work on obtaining metabolites of retinoic acid, especially hydroxylated regioisomers, is also under way. RECENT SELECTED PUBLICATIONS
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