Phaeantharinchlorid (1) hemmt im Plattendiffusionstest das Wachstum einiger grampositiver Bakterien. In einem Screening‐Verfahren des National Cancer Instituts in Bethesda/USA wurde weder für das Synthesezwischenprodukt 2 noch für den Diphenylether 3 eine cytostatische Wirkung gefunden. Am isolierten Ratten‐Ileum zeigt das Bisbenzylisochinolin 4 eine dem Papaverin identische spasmolytische Wirkung.

Racemates and Enantiomers of Basic Substituted 5-Phenylhydantoins. Syntheses and Antiarrhythmic Activity.-The synthesis of a variety of racemic 5-phenylhydantoins [cf. (III), (V), (VII)-(X)] vice Bucherer-Bergsreactions and their optical resolution following chemical procedures is described. The racemates and the enantiomers are evaluated for their antiarrhythmic activity. The enantiomers of compounds (V) and (VIII) show a negative inotropic actions. -(KNABE, J.; BALDAUF, J.; AHLHELM, A.; Pharmazie 52 (1997) 12, 912-919; Fachrichtung Pharm. Chem., Univ. des Saarlandes,

Prolonged administration of morphine for the treatment of chronic pain causes constipation requiring the use of laxatives, which may result in electrolyte deficits. Morphine-induced constipation is due to the binding of the drug to opioid receptors in the gastrointestinal tract and the brain, where it mimics the actions of enkephalins. The effect on the gastrointestinal tract seems to be more intense than the central effect. The particular pharmacokinetic of naloxone makes it possible to reduce or abolish the constipation that follows oral administration of morphine without markedly interfering with the central effect of morphine, i.e. analgesia. The results obtained with oral administration to rats of morphine and naloxone in aqueous solution have already been published [17]. Oral morphine in doses of 1, 2.5 and 5 mg/kg reduce the intestinal transit time in a dose-dependent manner (Fig. 2, filled circles). Doses of 10 and 20 mg/kg are as effective as 5 mg/kg. Naloxone 10 mg/kg administered together with morphine either prevented or attenuated the constipating effect of morphine (Fig. 2, open circles). Tail-flick latency was used as an indicator of analgesia in the animal experiment; it was significantly increased 1, 2 and 3 h after oral administration of morphine 2.5 mg/kg (Fig. 3, hatched columns). When naloxone 10 mg/kg was given with the morphine, there was no significant reduction in tail-flick latency (Fig. 3, cross-hatched columns). Thus, oral administration of naloxone in aqueous solution antagonized the constipating effect of morphine without interfering with the antinociceptive effect of morphine. Experiments carried out with oral administration to rats of slow-release naloxone instead of naloxone in aqueous solution have not so far been published. Slow-release naloxone 5 mg/kg abolished the slowing of intestinal transit caused by oral morphine 2.5 mg/kg (Fig. 4, left-hand columns). The increase in transit time following morphine 5 mg/kg was deminished by simultaneous oral administration of slow-release naloxone 3 and 5 mg/kg in a dose-dependent manner (Fig. 4, right-hand columns). The increase in tail-flick latency caused by morphine 2.5 mg/kg was reduced but not abolished by simultaneous administration of naloxone 5 mg/kg (Fig. 5). Slow-release naloxone 3 or 5 mg/kg reduced the duration without interfering with the maximum of the antinociceptive effect of morphine 5 mg/kg (Fig. 6). These results show that slow-release naloxone is more effective than naloxone in aqueous solution in antagonizing the effects of morphine: after oral administration of the slow-release preparation, even the central action of morphine is reduced. Provided that the anatomical organization of the haemorrhoidal veins in the rat is similar to that in man, slow-release naloxone will be carried by the matrix, to which it is absorbed further down in the gastrointestinal tract. It may thus even reach the rectum, from where, after having been absorbed, it bypasses the liver, enters the central nervous system and reduces the antinocic...

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