Ikezono K, Fujita S, Umezato M, Hosoki E, Toba Y, Kusunoki A, Shintani S
Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan.
Arzneimittelforschung. 1992 Oct;42(10):1200-11.
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)
研究了一种新型血管扩张剂氟司喹南（7-氟-1-甲基-3-(甲基亚磺酰基)-4(1H)-喹诺酮，BTS 49 465，CAS 76568-02-0）对中枢神经系统、躯体神经系统、自主神经系统和平滑肌、消化系统及其他器官的药理作用。1. 中枢神经系统：氟司喹南口服剂量超过30mg/kg时可抑制乙酸诱导的小鼠扭体反应，口服100mg/kg时可降低小鼠体温并使自发活动略有减少。然而，氟司喹南对戊巴比妥诱导的催眠、利血平诱导的体温过低及运动协调几乎没有影响，且在小鼠中缺乏抗惊厥和镇痛活性。氟司喹南对大鼠的一般行为影响较小，对兔的自发脑电图和脑电图唤醒反应无任何影响。2. 躯体神经系统：氟司喹南不会引起小鼠肌肉松弛，对猫的神经肌肉传递影响较小。通过抑制豚鼠角膜反射未表现出局部麻醉活性。3. 自主神经系统和平滑肌：氟司喹南浓度超过3×10(-5)mol/l时可使豚鼠离体气管松弛，但其效力与异丙肾上腺素相比非常弱。氟司喹南浓度高于10(-4)mol/l时可抑制妊娠大鼠离体子宫的自发运动，静脉注射30mg/kg时可抑制非妊娠大鼠子宫在体内的运动。氟司喹南似乎对去甲肾上腺素、5-羟色胺、乙酰胆碱或组胺无任何作用。这一点得到以下事实的支持：在10(-4)-3×10(-3)mol/l浓度下，观察到氟司喹南对去甲肾上腺素诱导的大鼠离体主动脉和输精管收缩、5-羟色胺诱导的大鼠离体胃收缩、乙酰胆碱、组胺和氯化钡诱导的豚鼠离体回肠收缩以及催产素诱导的非妊娠大鼠离体子宫收缩均无竞争性抑制作用。然而，氟司喹南作为血管舒张剂比其他平滑肌舒张剂更有效。静脉注射高剂量30mg/kg时，氟司喹南对猫节前交感神经刺激诱导的瞬膜收缩有轻微抑制作用。4. 消化系统：口服100mg/kg氟司喹南可抑制小鼠肠道推进，静脉注射30mg/kg可抑制大鼠胃和十二指肠的自发运动。（摘要截于400字）
