Possible steady-state concentrations of tetrahydroisoquinolines in brain after the consumption of ethanol

Dopamine-derived tetrahydroisoquinolines such as salsolinol and tetrahydropapaveroline have been implicated in alcohol-related problems. Though their infusion into the brain can induce a rat to increase its alcohol consumption, it is not known whether the compounds actually form in vivo. Few investigators have been able to extract the compounds or their metabolites from tissue or urine. One notable exception is reported by Collins et al. (Science 206: 1184--1186; 1979), who found that alcoholics excrete 140 micrograms/24 h of O-methyl salsolinol and salsolinol. Using that value as the rate of salsolinol formation in brain, it was possible to estimate the steady-state concentration that could be expected to be found in brain. It was assumed that the rate of synthesis is equal to the rate of removal from tissue. Thus, the concentration is simply vf/kd, where vf is the rate of formation and kd is the rate constant for the disappearance from brain. It is necessary to estimate the concentration of dopamine and aldehyde in brain to determine the rate of formation. The realistic upper limits for salsolinol and tetrahydropapaveroline in brain are ca. 1 ng/g brain tissue. These values are below the level of detection commonly employed.