Differences in lithium effects in depressed and healthy subjects.
To evaluate the neurotransmitter actions of lithium without the confounding biochemical abnormalities associated with affective disorders, Li was given to 12 hospitalized healthy young men. After a 600-mg loading dose, subjects were placed on "therapeutic" Li doses averaging 1225 +/- 300 mg for 1 wk, reaching steady-state plasma levels of 0.82 +/- 0.17 mEq/l. Cardiovascular function at rest and diastolic blood pressure and pulse on standing were not altered by Li. Average baseline plasma norepinephrine (NE) concentration in the supine position (1.07 +/- 0.50 pmol/ml) did not change after 1 wk of Li dosing (1.16 +/- 0.57 pmol/ml). There was similar variability, without mean change, in plasma NE increments after orthostatic challenge and in plasma 3-methoxy-4-hydroxyphenylglycol concentrations before and during Li dosing. Urine volume was stable throughout the week of drug dosing, during which daily NE excretion was constant. In contrast to earlier data obtained in patients with depression receiving Li, there were no Li-related decrements in average whole-body NE or dopamine turnover. Mean daily urinary excretion rates of serotonin and its major metabolite 5-hydroxyindoleacetic acid did not change throughout the study. Our and other studies suggest that Li has a corrective action in patients with depression and hypothesized neurotransmitter abnormalities, but Li does not affect individuals without affective disorders.
Rudorfer
M V
MV
Karoum
F
F
Ross
R J
RJ
Potter
W Z
WZ
Linnoila
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000652:urine; D000328:Adult; D003863:Depression / Q000188:drug therapy*; D004298:Dopamine / Q000652:urine; D006719:Homovanillic Acid / Q000652:urine; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D008094:Lithium; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid