Dopamine-norepinephrine interaction in hyperactive boys treated with d-amphetamine.

We studied the relationship between the excretion of 3-methoxy-4-hydroxyphenylglycol, the main metabolite of central nervous system norepinephrine, and homovanillic acid, the main metabolite of dopamine, in 16 hyperactive boys and ten controls who were admitted to a clinical research center. We further examined the effect of d-amphetamine (0.5 mg/kg body weight daily for two weeks) on that relationship. The correlation coefficients r between MHPG and HVA excretion were significantly negative in hyperactive boys and significantly positive in controls when the relational effects of age, body surface, and 24-hour urinary creatinine with MHPG and HVA excretion were removed. Furthermore, the correlation coefficient r in hyperactive boys and in responders at baseline differed significantly from the correlation coefficients in post-treatment and in controls. The post-treatment correlation coefficient in hyperactive boys and responders did not differ from that in controls. We suggest an altered relationship between DA and NE activity in hyperactive children. Meaningful interpretation of the data should await the availability of more information on the amount of contribution of central NE and DA metabolism to urinary MHPG and HVA in both hyperactive and normal children.

Norepinephrine metabolism and clinical response to dextroamphetamine in hyperactive boys.

The 24-hour urinary catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol, normetanephrine, and metanephrine were measured in 23 hyperactive boys and 13 matched healthy controls. The hyperactive children excreted lower MHPG and higher NM (low MHPG/NM ratio) amounts than in controls. The administration of d-amphetamine in the dose of 0.5 mg/kg body weight divided over two doses daily for two weeks decreased MHPG excretion in the hyperactive children. When the hyperactive children group was divided into drug responders and nonresponders according to their pre- and post-treatment scores on the Conners Teacher Questionnaire, d-amphetamine administration decreased MHPG excretion in the responders and did not change it in the nonresponders. Percent decrease in MHPG excretion correlated significantly with percent change in the hyperactivity factor of the questionnaire on the Spearman Rank Order Correlation Coefficient. Pretreatment urinary metabolites did not differentiate the responders from nonresponders. It is suggested that a relationship between CNS norepinephrine metabolism and hyperactivity exists and that d-amphetamine may achieve its therapeutic action in hyperactive children by altering CNS NE metabolism.