General pharmacological properties of the new vasodilator flosequinan.
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)
Ikezono
K
K
Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan.
Fujita
S
S
Umezato
M
M
Hosoki
E
E
Toba
Y
Y
Kusunoki
A
A
Shintani
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D001522:Behavior, Animal / 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; D009130:Muscle, Smooth / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014563:Urodynamics / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007509:Irritants; D011804:Quinolines; D014665:Vasodilator Agents; C047316:flosequinan