After
intraventricular injection of norepinephrine-H3, the concentration of
norepinephrine, of
normetanephrine and of the deaminated
catechols in rat brains was determined, following action of
imipramine,
desmethylimipramine,
chlorpromazine,
lithium chloride or
cocaine. Following administration of
imipramine,
desmethylimipramine, and
chlorpromazine,
norepinephrine concentration decreased significantly at first, had distinctly increased 4.5 hours after
imipramine and
desmethylimipramine but was normal once again after
chlorpromazine.
Normetanephrine concentration increased after
imipramine and
desmethylimipramine but was unchanged after
chlorpromazine. Under the effect of these drugs, the deaminated
catechols showed no changes compared with control values.
Cocaine resembled the
antidepressants, but the amount of deaminated compounds was reduced.
Lithium chloride, on the other hand, increased the concentration of deaminated
catechols under certain conditions, reduced
normetanephrine concentration but did not influence
norepinephrine concentration. In addition to the animal experiments, the following data of six patients with an "
endogenous" depression were recorded over a period of several weeks: the clinical findings by means of the Hamilton Depression Rating Scale, and the excretion of
normetanephrine and of
vanillylmandelic acid (VMA) in the urine before, during and
after treatment with
imipramine. The
therapy led to a significant reduction of VMA; however, this reduction cannot be correlated with an improvement in the clinical findings. On the other hand, excretion of
normetanephrine is apparently not dependent on the administration of
imipramine but seems to reflect the clinical state, since improvement of the depression was regularly combined with an increased excretion of
normetanephrine.