Naunyn-Schmiedeberg's archives of pharmacology
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Naunyn Schmiedebergs Arch. Pharmacol. · Dec 1978
Increased digitoxin cleavage by liver microsomes of spironolactone-pretreated rats.
Pretreatment of rats with spironolactone caused an fourfold increased cleavage rate of the sugar chain of digitoxin (dt-3) in vitro yielding digitoxigenin-bis-digitoxoside. This was due to an enhanced, cyt. ⋯ In contrast to the effects of spironolactone no increase of metabolism could be observed after phenobarbital pretreatment. From our results it may be concluded that the enhanced dt-3 metabolism in vivo is mainly caused by spironolactone inducible monoxygenases which catalyse the oxidation of the terminal sugar.
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Naunyn Schmiedebergs Arch. Pharmacol. · Apr 1977
The effects of an inhibitor of phenylethanolamine N-methyltransferase upon stimulated adrenal catecholamine release and excretion in the rat.
SK&F 64139, an inhibitor of adrenal phenylethanolamine N-methyltransferase (PNMT), was found to significantly decrease 2-deoxy-D-glucose (2-DG) induced epinephrine excretion in the conscious rat under conditions where the former agent was administered chromically at 50 and 200 mg/kg/day over a 12-day period and 2-DG was administered after 3, 7 and 11 days of treatment. The reduced epinephrine output caused by SK&F 64139 in response to 2-DG was accompanied by an increased norepinephrine excretion pattern at 200 mg/kg/day of the compound. The reductions in epinephrine excretion were also associated with significant decreases in adrenal epinephrine and increases in the norepinephrine content.
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Naunyn Schmiedebergs Arch. Pharmacol. · Jul 1976
Alterations of dopaminergic neurotransmission after chronic morphine treatment: pre- and postjunctional studies in striatal tissue.
Repeated morphine administration reversed the acute effects of morphine in rats, e.g. catalepsy and akinesia, and induced symptoms suggesting an activation of dopaminergic mechanisms. In morphine-withdrawn rats, the potency or intrinsic activity of dopamine in stimulating the synthesis of cyclic AMP in striatal homogenates was not significantly altered. ⋯ The results suggest that chronic morphine administration to rats increases the dopaminergic neurotransmission in brain by a pre-synaptic (prejunctional) mechanism, probably reflecting some kind of adaptation to the acute morphine action, which decreases the dopaminergic neurotransmission. The nigro-straital dopaminergic system, therefore, seems to be a good model to study acute morphine actions and mechanisms of morphine dependence at the cellular level.