title: General pharmacological properties of the main metabolite of flosequinan.
abstract: 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)
authors.affiliation: Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Ikezono
authors.forename: M
authors.initials: M
authors.lastname: Umezato
authors.forename: E
authors.initials: E
authors.lastname: Hosoki
authors.forename: Y
authors.initials: Y
authors.lastname: Toba
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.forename: A
authors.initials: A
authors.lastname: Kusunoki
authors.forename: S
authors.initials: S
authors.lastname: Shintani
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007509:Irritants / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010525:Peripheral Nerves / Q000187:drug effects; D011247:Pregnancy; D011804:Quinolines / Q000378:metabolism* / Q000494:pharmacology; D015363:Quinolones / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014563:Urodynamics / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007509:Irritants; D011804:Quinolines; D015363:Quinolones; C047316:flosequinan; C047317:flosequinoxan