GENERAL PHARMACOLOGY OF T-3761, A NEW ORAL QUINOLONE ANTIBACTERIAL AGENT (1) EFFECT ON THE CENTRAL NERVOUS SYSTEM

• Published in: Japanese journal of antibiotics Vol. 48; no. 5; pp. 692 - 705
• Main Authors: FURUHATA, KUNIKAZU, HIRAIWA, TORU, ONO, SATOSHI, TANAKA, KEIICHI, SHIMOTORI, TOMOYA, MAKINO, SHINJI, KITAMURA, KAZUNORI, AIKAWA, YUKIHIKO, IZUMI, YOSHINOBU, KIMURA, TATSUO, NAKADA, RYOKO, HIRAI, SHIRO
• Format: Journal Article
• Language: Japanese
• Published: Japan Japan Antibiotics Research Association 01.05.1995
• Subjects: Animals; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - adverse effects; Anti-Infective Agents - pharmacology; Cats; Central Nervous System - drug effects; Dose-Response Relationship, Drug; Female; Fluoroquinolones; Male; Mice; Mice, Inbred ICR; Oxazines - administration & dosage; Oxazines - adverse effects; Oxazines - pharmacology; Rats; Rats, Wistar
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.48.692

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 respones, reserpine-induced hypothermia and ptosis in mice at oral doses of 100,300 and 1,000mg/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 100mg/kg. 3. Convulsions were not observed in mice after any oral combinations of T-3761 at a dose of 200 or 1,000mg/kg with 14 different nonsteroidal anti-inflammatory drugs (NSAIDs) including fenbufen. 4. An oral combination of T-3761 even at a higher does of 3,000mg/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 10-4M 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.