[General pharmacology of T-3761, a new oral quinolone antibacterial agent (1). Effect on the central nervous system].
General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the central nervous system were investigated in laboratory animals. The results obtained are summarized as follows. 1. T-3761 exerted no significant effects on spontaneous motor activity, motor coordination, pentobarbital-induced hypnosis, electroshock-, pentetrazole- or strychnine-induced convulsion, acetic acid-induced writhing responses, reserpine-induced hypothermia and ptosis in mice at oral doses of 100, 300 and 1,000 mg/kg. The same oral doses of T-3761 exerted no significant effects on body temperature and passive avoidance response in rats. 2. T-3761 had no effects on EEG in cats and spinal reflex in rats at intravenous doses of 10, 30 and 100 mg/kg. 3. Convulsions were not observed in mice after any oral combinations of T-3761 at a dose of 200 or 1,000 mg/kg with 14 different nonsteroidal anti-inflammatory drugs (NSAIDs) including fenbufen. 4. An oral combination of T-3761 even at a higher doses of 3,000 mg/kg with 4-biphenylacetic acid (BPAA) which is a principally active metabolite of fenbufen also did not induce convulsions in mice. 5. T-3761 did not inhibit GABA receptor binding in rat brain synaptic membranes at 10(-4) M in either the absence or presence of BPAA. These results suggest that T-3761 is an antibacterial agent which would be unlikely to produce any side effects on the central nervous system and to produce convulsion when combined with NSAIDs in clinical use.
Furuhata
K
K
Research Laboratories, Toyama Chemical Co., Ltd.
Hiraiwa
T
T
Ono
S
S
Tanaka
K
K
Shimotori
T
T
Makino
S
S
Kitamura
K
K
Aikawa
Y
Y
Izumi
Y
Y
Kimura
T
T
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010078:Oxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010078:Oxazines; C078052:pazufloxacin