Pharmacological properties of centrally administered ouabain and their modification by other drugs

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Abstract
1 Ouabain given by intracerebroventricular injection to mice in small doses (0·1–0·4 μg) produced a dose related depression of central nervous activity, characterized by a reduction in spontaneous locomotor activity, hypothermia, catalepsy and ptosis, lowered body posture and lack of response to external stimuli. Doses above 0·4 μg were excitatory, convulsant and lethal. 2 The depressant effects could be antagonized by (+)-amphetamine, desmethylimipramine, dibutyryl cyclic 3′5′-adenosine monophosphate and caffeine. 3 The MAO inhibitor nialamide produced only a small antagonism of ouabain, resulting in a greater rate of recovery from the depressant effects of ouabain. 4 The depressant effects were associated with a marked elevation of whole-brain dopamine levels with little change in noradrenaline or 5-hydroxytryptamine. 5 The dopamine-β-hydroxylase inhibitor sodium diethyldithiocarbamate, administered by intracerebroventricular injection, produced effects qualitatively similar to those seen after ouabain. 6 An interference with central transmitter function is postulated as a possible mode of action of intracerebroventricularly injected ouabain.