THE EFFECTS OF LITHIUM ON NOREPINEPHRINE TURNOVER AND METABOLISM: BASIC AND CLINICAL STUDIES

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Abstract
In a series of experiments in rats, acute or short term (3 days) administration of lithium chloride was observed to increase the turnover of norepinephrine in the brain, as evidenced by the more rapid disappearance of intracisternally administered norepinephrine-8H from brain. Further findings from these experiments suggest that the increase in norepinephrine turnover produced by lithium occurs as a result of enhanced intraneuronal release, rather than extraneuronal discharge, of norepinephrine. In a longitudinal investigation of a manic patient studied prior to treatment with lithium carbonate and for more than 6 months during treatment, a transient increase in the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), lasting several days, was observed at the onset of lithium administration; however, over the subsequent course of treatment with lithium carbonate, there was a gradual decrease in the excretion of MHPG as well as norepinephrine, normetanephrine, and 3-methoxy-4-hydroxymandelic acid (VMA). These basic and clinical findings, taken in conjunction with observations of other investigators, suggest that the long term effects of lithium on norepinephrine turnover are different from the short term effects, and that a transient increase in norepinephrine turnover may be observed only during the initial phase of lithium administration.

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