Sean Kocur wins Scholarship award at RISE.
Heavy, chronic consumption of alcohol (ethanol) causes a constellation of adverse effects on health and is associated with a withdrawal syndrome that promotes addiction. Also, motor vehicle accidents and other events associated with alcohol intoxication are a major problem. On the other hand, many people consume alcohol in moderate doses on an occasional basis with no apparent ill effects, presumably because they appreciate its mild euphorigenic and anxiolytic properties, and much evidence supports the view that a glass of red wine a day benefits the cardiovascular system. In spite of decades of research on what is surely mankind’s oldest drug, the exact ways in which alcoholic beverages induce all of their many effects are not completely understood. The direct actions of ethanol on targets such as glutamate and GABA receptors are probably responsible for much of the drug’s psychoactivity. However, it is possible that metabolites of alcohol are responsible for some of the effects, and alcohol metabolites also have utility as forensic biomarkers of alcohol consumption, that can, for example, help determine responsibility in motor vehicle and industrial accidents. Such metabolites include tetrahydroisoquinoline compounds that are formed from reaction of the proximal ethanol metabolite, acetaldehyde, with monoamines such as dopamine. While some of these compounds have been the sporadic focus of attention from alcohol researchers over the last half-century, we feel the time is ripe for a reevaluation of their forensic and psychoactive potentials, and have developed an LC/MS/MS system that will permit us to quantify concentrations of tetrahydroisoquinolines and related compounds in animal tissues. We are particularly interested in 3-carboxysalsolinol, the TIQ derived from acetaldehyde and L-DOPA, and in preliminary work synthesized this compound with and without deuterium substitution. Using the deuterated compound as an internal standard, we demonstrated the presence of 3CS and it methoxylated derivative in mouse brain, and are now embarking on LC/MS/MS studies to thoroughly characterize its pharmacokinetics.