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The effects of iontophoretically applied Na+-, K+-dependent adenosinetriphosphatase (Na+,K+-ATPase) (EC 3.6.1.3) inhibitors (ouabain, digitoxin, digitoxigenin, strophanthin K, strophanthidin, thevetin A and B, ethacrynate, and harmaline) on the depression of rat cerebral cortical neurones by noradrenaline, 5-hydroxytryptamine, and histamine have been(More)
OBJECTIVES In a randomized, double-blind, crossover design, we compared the efficacy of sildenafil with placebo in patients with primary pulmonary hypertension (PPH). The primary end point was the change in exercise time on treadmill using the Naughton protocol. Secondary end points were change in cardiac index and pulmonary artery systolic pressure as(More)
BACKGROUND Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point. We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial. METHODS We randomly assigned(More)
Histamine (H) and H1 agonists 2-pyridylethylamine (PEA) and 2-methylhistamine (2-MH) produced a greater depression of the corticospinal and unidentified rat cerebral cortical neurones than did 4-methylhistamine (4-MH), an H2 agonist. Mepyramine antagonized the effects of 2-MH, PEA and H, and partially antagonized the depression induced by 4-MH. Metiamide(More)
Previous observations from our laboratory indicate that metiamide is a specific histamine antagonist in rat cerebral cortex. In view of the recent finding that histamine levels and L-histidine decarboxylase (EC 4.1.1.22) activity in cerebral cortex decrease following disruption of the ipsilateral medial forebrain bundle (MFB), the present investigation was(More)
In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide, and oxygen, the depressant actions on the cerebral cortical neurones of iotophoretically applied 5-hydroxytryptamine (5-HT) but not of noradrenaline, histamine, AMP Ca2+, and gamma-aminobutyric acid were antagonized by metergoline. These observations indicate that metergoline may be a(More)
Recent observations made in our laboratory have shown that metergoline is a selective 5-hydroxytryptamine (5-HT) antagonist in the cerebral cortex. Fluoxetine is a reportedly selective 5-HT neuronal uptake blocker. In the present investigation these drugs have been used to examine the existence of a putative 5-HT input to the cerebral cortex. In rats(More)
Recurrent inhibition of the extensor (quadriceps) monosynaptic reflex (MSR) was antagonized by a 5-hydroxytryptamine (5-HT) precursor, 5-hydroxytryptophan (5-HTP, 75 mg/kg), and a specific 5-HT neuronal uptake blocker, fluoxetine-HC1 (Lilly 110140, 0.25-6 mg/kg), in unanaesthetized decerebrate cats. This inhibition of the flexor (posterior(More)