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[General pharmacology of traxanox sodium. I. Effects on the central, somatic, and autonomic nervous systems, digestive system, urologic organs, and reproductive system].

Traxanox at the upper dose of 300 mg/kg, p.o., showed no effect on the somatic and autonomic nervous systems in the various tests. This agent caused some relaxation of the guinea pig tracheal strip in the resting tone at a concentration of 10(-6)M or more; however, its activity was less potent than that of isoproterenol and paraverine. Traxanox had no competitive antagonistic action against chemical mediators. Treatment of rats with this agent (3 mg/kg, i.v., or 10 mg/kg, s.c.) resulted in an inhibition of gastric (acid) secretion. Intravenous injections of traxanox (1-10 mg/kg) in dogs caused an immediate but transient inhibition of gastric and jejunal movement, and after a short time, slight potentiation of the latter; however, pretreatment with atropine prevented this latter potentiation. In the in vitro test, 10(-4)M traxanox caused contraction of the guinea pig ileum, a response which was inhibited by atropine. Traxanox (300 mg/kg, p.o.), however, did not show any effects on gastrointestinal propulsion in mice, nor did it have any effect on the gastrointestinal mucosa, gastric ulcers or bile secretion in rats. Traxanox (300 mg/kg, p.o.) showed a diuretic action in both normal and adrenoectomized rats. This action, however, was not observed in the rats treated with indomethacin (1 mg/kg, i.p.). This agent (10 mg/kg, i.v.) suppressed the spontaneous uterine contractions of pregnant rats in some cases. These findings suggest that traxanox at doses (1-5 mg/kg, p. o.) showing antiallergic activity has little effect on the central, somatic and autonomic nervous systems, digestive system, urinary organs and reproductive organs.

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[Effects of cadralazine on the respiration, circulation, kidney, autonomic nervous system, digestive system, blood and so on].

The general pharmacological effects of cadralazine and its major metabolite ISF 2405 were studied by comparing them with those of hydralazine. Cadralazine at 3.0 mg/kg, i.v., increased respiratory movement and heart rate and decreased blood pressure in cats. Cadralazine at 3.0 mg/kg, i.v., inhibited the hypertensive response induced by adrenaline, but showed little effect on the hypotensive response induced by acetylcholine in cats. Cadralazine and ISF 2405 at 10(-4) g/ml had negative chronotropic effects on isolated guinea-pig atria. The drug at 2.5 mg/kg, p.o., inhibited the passage of BaSO4 in the gastrointestinal tract in mice. The drug at 5.0 mg/kg, i.d. or more inhibited gastric secretion in rats. Cadralazine, except at higher doses, had little effect on spontaneous gastric motility and uterine spontaneous movement in rats. Cadralazine at 2.5 mg/kg, p.o., or more reduced or tended to reduce urine volume and urinary excretion of electrolytes. The drug showed little effect on coagulation and osmotic fragility in blood cell in rats nor on hemolysis and platelet aggregation in rabbits. ISF 2405, however, showed slight or moderate influence on hemolysis at concentrations as high as 0.01-1.0%. Cadralazine at 5.0 mg/kg, p.o. or more antagonized carrageenin-induced hind paw edema in rats. In conclusion, these effects of cadralazine were found to be qualitatively identical with those of hydralazine.

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