Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The general pharmacological profile of 7-fluoro-1-methyl-3-(methylsulfonyl)- 4(1H)-quinolone BTS 53 554, CAS 76568-68-8), the main metabolite of a new vasodilator, flosequinan (BTS 49 465), was investigated. 1. The central nervous system: BTS 53 554 at the dose of 30 mg/kg i.v. caused an increase in respiratory rate and a sedation in general behavior in rats. The drug also inhibited acetic acid-induced writhing and slightly decreased normal body temperature in mice. However, the drug at the doses up to 30 mg/kg i.v. had little effect on the spontaneous movement, hexobarbital-induced hypnosis, reserpine-induced hypothermia and motor coordination in mice. The drug showed neither anticonvulsant nor analgesic actions in mice. Furthermore, it had no effect on the spontaneous EEG, sleep-wakefulness cycle and EEG arousal response in rabbits at doses up to 10 mg/kg intravenously. 2. The somatic nervous system: BTS 53 554 induced no muscle relaxation in mice and exerted no local anesthetic action in guinea pigs by corneal reflex method. In addition, it had little effect on the neuromuscular transmission in cats. 3. The autonomic nervous system and smooth muscle: BTS 53 554 showed no effect on the sympathetic ganglionic transmission in cats. In isolated smooth muscles, at doses up to 10(-3) mol/l it showed little effect on the acetylcholine- or barium chloride-induced contraction of guinea-pig ileum, norepinephrine-induced contraction of rat vas deferens or oxytocin-induced contraction of nonpregnant rat uterus. However, it inhibited non-competitively norepinephrine-induced contraction of isolated rat aorta at 10(-4) mol/l or more and serotonin-induced contraction of isolated rat fundus at 3 x 10(-4) mol/l or more. In the isolated guinea-pig ileum, the drug slightly inhibited the histamine-induced maximal contraction at 10(-3) mol/l. These results suggest BTS 53 554 had no specific effect on norepinephrine, serotonin, acetylcholine or histamine. The drug relaxed isolated guinea-pig trachea at 3 x 10(-5) mol/l or more and inhibited the spontaneous movement of isolated pregnant rat uterus at 10(-4) mol/l or more, although these actions were extremely weaker than those of isoproterenol (isoprenaline). BTS 53 554 also showed a slight inhibition of uterus movement in anesthetized rats at 30 mg/kg intravenously. 4. The digestive system: BTS 53 554 tended to inhibit the gastrointestinal propulsion in mice and showed a slight inhibition of gastric and intestinal motilities in rats at 10 mg/kg intravenously.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:General pharmacological properties of the main metabolite of flosequinan. 133 57

Pharmacological effects of a new vasodilator, flosequinan (7-fluoro-1-methyl-3-(methylsulfinyl)-4(1H)-quinolone, BTS 49 465, CAS 76568-02-0) on the central nervous system, somatic nervous system, autonomic nervous system and smooth muscle, digestive system and miscellaneous organs were investigated. 1. The central nervous system: Flosequinan inhibited acetic acid-induced writhing at doses of more than 30 mg/kg p.o. and decreased body temperature and tended to decrease spontaneous movement slightly in mice at a dose of 100 mg/kg p.o. However, flosequinan had little effect on hexobarbital-induced hypnosis, reserpine-induced hypothermia and motor coordination and lacked anticonvulsant and analgesic activities in mice. Flosequinan had little effect on general behavior in rats and did not have any effect on spontaneous EEG and EEG arousal response in rabbits. 2. The somatic nervous system: Flosequinan did not cause muscle relaxation in mice and had little effect on neuromuscular transmission in cats. No local anesthetic activity was exhibited through inhibition of the corneal reflex in guinea pigs. 3. The autonomic nervous system and smooth muscle: Flosequinan produced a relaxation of the isolated trachea of guinea pigs at concentrations of more than 3 x 10(-5) mol/l, but its potency was very weak in comparison with that of isoproterenol (isoprenaline). Flosequinan inhibited spontaneous motility of the isolated uterus of pregnant rats at concentrations higher than 10(-4) mol/l and the motility of the uterus of non-pregnant rats in vivo was inhibited at 30 mg/kg i.v. Flosequinan does not seem to exert any on norepinephrine, serotonin, acetylcholine or histamine. This is supported by the fact that at concentrations of 10(-4)-3 x 10(-3) mol/l non-competitive inhibition was observed with regard of the contractions of the isolated aorta and vas deferens of rats induced by norepinephrine, the contraction of isolated rat stomach induced by serotonin, the contraction of isolated guinea-pig ileum induced by acetylcholine, histamine and barium chloride and the contraction of the isolated uterus of non-pregnant rats induced by oxytocin. However, flosequinan was more potent as a relaxant of vascular than of these other smooth muscles. The drug was slightly inhibitive at a high dose of 30 mg/kg i.v. with regard of the contraction of nictitating membrane induced by stimulation of preganglionic sympathetic nerve in cats. 4. The digestive system: Flosequinan at 100 mg/kg p.o. inhibited intestinal propulsion in mice and inhibited spontaneous motility of stomach and duodenum of rats at a dose of 30 mg/kg i.v.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:General pharmacological properties of the new vasodilator flosequinan. 147 41