These results suggest that an excessive response to sympathetic nerve stimulation, which is mainly mediated via alpha(1A)-adrenoceptor, in the hypertrophied prostate gives rise to detrusor overactivity. Furthermore, the alpha(1A)-adrenoceptor selective antagonist KMD-3213 would be suitable for improving irritative symptoms in patients with benign prostatic hyperplasia.

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This study aimed to examine the eŠects of banana juice on levodopa bioavailability in rats. When a levodopa preparation (EC-Doparl tablets) was orally administered with banana juice made by mixing with a fresh banana and water, there were signiˆcant decreases in C max (17.4±2.5 vs. 8.6±3.1 mg/ml; a＝0.05) and AUC (1882.8±49.2 vs. 933.5± 286.6 mg・min/ml; a＝0.05) for levodopa. On the other hand, administration of the levodopa preparation with a commercial beverage containing 10％ banana juice resulted in no signiˆcant change in C max or AUC. These results indicate that concomitant intake of levodopa preparations with banana juice, but not with a commercial banana beverage, may cause a drug-food interaction reducing levodopa bioavailability, and we should pay attention to such interactions during levodopa therapy for patients with Parkinson's disease.

The aim of this study was to assess the cardiovascular effects of silodosin (CAS 160970-54-7, (-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy) phenoxy]ethyllamino)propyll-2,3-dihy-dro-1H-indole-7-carboxamide, KMD-3213), a potent selective alpha1A-adrenoceptor (AR) antagonist used for the treatment of dysuria. In conscious dogs, orally administered silodosin, at doses (0.2, 2 and 20 mg/kg) considerably higher than the pharmacologically effective dose, decreased blood pressure. These doses, however, had no effects on heart rate or on the electrocardiogram (PR interval, QRS interval, QT interval or QTc). In addition, the cardiac effects of silodosin were evaluated in an in vitro electrophysiological study. Silodosin inhibited the human ether-a-go-go-related gene (HERG) tail current, leaving a residual tail current of 45 % control at 10 micromol/L. However, the concentration that inhibited the HERG tail current was considerably higher than its affinity for alphal-ARs. These results suggest that while the alpha1B-AR subtype is mainly involved in the regulation of blood pressure, the alphalA-AR subtype is not. There seems to exist no evidence of a correlation between the function of alphal-AR and ECG changes reflecting inhibition of the HERG current. The cardiovascular profile of silodosin suggests therefore that it is a safe and well-tolerated drug.

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Abstract-Characteristicsof the analgesic action of phenylethylamine derivatives, amphetamine, phenylethylamine (PEA), hydroxyphenylethylamine (OHPEA) and hydroxyphenylalanine (OHF), were examined. Pain threshold of mice was measured by using the hot plate method.OHPEA (50 mg/kg), amphetamine (0.5-8 mg/kg) or PEA (50 mg/kg) produced an analgesic effect in the absence of MAO inhibitor, and the analgesia was reversed by naloxone (5 mg/kg) or reserpine (2 mg/kgx2). Ten mg/kg of PEA, 250 mg/kg of OHF and 10 mg/kg of OHPEA could not produce detectable analgesia, but they revealed analgesic activity when mice were pretreated with pargyline (100 mg/kg).