Attempts to characterize the neurotransmitter systems in man have focused on quantification of the neurotransmitters (seronin 5HT), norepinephrine (NE), dopamine (DA), and several metabolites of these monoamines in various body fluids (urine, plasma, CSF). These neurotransmitter systems are suspected to be functioning abnormally in a variety of disorders (alcoholism, depression, schizophrenia, etc.). In order to understand the meaning of measuring concentrations of neurotransmitters and their metabolites, it is necessary to understand their pharmacokinetics in different body compartments. a) Plasma and CSF concentrations, as well as 24 hour urinary measures of NE, DA and 5HT and their metabolites (VMA, MHPG, NM, 5HIAA, HVA) were collected in placebo treated, depressed subjects, alcoholics and healthy volunteers. Samples were also collected in depressed subjects following treatment with antidepressants. Utilizing these data, a model was formulated which describes the disposition of MHPG. b) Rat liver perfusion using two NE metabolites, NM and MHPG, will be used to determine the fraction of a metabolite being transformed by each of several metabolic pathways. A better understanding of these relationships will help identify differences in formation, metabolism and elimination of these neurotransmitters in humans. This will offer insight into the functioning of these systems, and into the abnormalities of function that result in the previously observed abnormal concentrations of these neurotransmitters and their metabolites in certain disease states such as alcoholism and alcohol withdrawal.
