[General pharmacology of T-3262, a new pyridonecarboxylic acid].
General pharmacological activities of (+/-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dih ydro- 4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262), which is a new pyridonecarboxylic acid, were examined with the following results. 1. Central nervous system: T-3262 did not show any significant pharmacological effects at oral doses of 100-1,000 mg/kg but caused slow waves in spontaneous EEG in cats at intravenous doses of 10-30 mg/kg. 2. Respiratory and cardiovascular system: T-3262 produced little effect in normotensive rats and anesthetized rabbits at oral doses of 100-1,000 mg/kg and intravenous doses of 3-30 mg/kg, respectively. But T-3262 caused, dose-dependently, an increase of respiratory rate, hypotension, decrease of heart rate and changes in ECG patterns (elevation of T waves, slow amplitudes of QRS complexes and prolongation of RR interval, etc.) in anesthetized dogs at intravenous doses of 3-10 mg/kg. 3. Renal functions: T-3262 increased electrolyte excretions at oral doses of 300-1,000 mg/kg but did not affect PSP excretion in rats. 4. Autonomic nervous system and smooth muscle organs: T-3262 exerted slight inhibition of gastric output in rats and slight miosis in mice at an oral dose of 1,000 mg/kg. But T-3262 did not affect the contraction of nictitating membrane in anesthetized cats at intravenous doses of 1-30 mg/kg. T-3262 increased spontaneous motilities of isolated stomach, ileum and uterus, but decreased that of isolated colon at concentrations of 10(-5)-10(-4) g/ml. 5. Hematological examinations: T-3262 did not show any significant effects on bleeding time, blood coagulation, platelet aggregation and blood glucose level in rats at oral doses of 100-1,000 mg/kg. 6. Miscellaneous effects: T-3262 exerted slight inhibitions of gastric secretion and of carrageenin-induced hind paw edema in rats at a dose of 1,000 mg/kg administered intraduodenally and orally, respectively. T-3262 did not affect neuromuscular junction and bile secretion in rats at intravenous doses of 3-30 mg/kg and oral doses of 100-1,000 mg/kg, respectively. From these results, it can be assumed that T-3262 has a wide safety margin as an oral antibacterial agent.
Research Laboratory, Toyama Chemical Co., Ltd.
S
S
Hirai
T
T
Hiraiwa
H
H
Arai
S
S
Ono
K
K
Tanaka
K
K
Hashiba
Y
Y
Nakada
K
K
Goden
K
K
Tanada
M
M
Maekawa
D042462:4-Quinolones; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009287:Naphthyridines; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects
D042462:4-Quinolones; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C055185:tosufloxacin