title: Pharmacological properties of a new fluoroquinolone on the central nervous system in rodents.
abstract: The pharmacological effects of the novel fluoroquinolone 7-(1R,4R-2,5-diazebicyclo[2.2.1]heptan-2-yl)-1-(1,1-dimethyl )ethyl-6-fluoro - 4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (BMY-40062, CAS 116143-32-9) on central nervous system were investigated in mice and rats, in comparison in some cases with those of reference quinolones. BMY-40062 showed no effect on general behavior, spontaneous activity, body temperature and neuromuscular coordination in rats at the doses of 1000 and 250 mg/kg. None of the quinolones tested including BMY-40062 modified the seizures induced by bicuculline, a specific GABA A antagonist. BMY-40062 and ciprofloxacin did not consistently influence the pentetrazol-induced convulsions. On the contrary, pefloxacin exhibited a marked convulsivant activity. In the fenbufen (non-steroidal anti-inflammatory drug)-induced seizure model, BMY-40062 showed no effect. Enoxacin, norfloxacin followed by ciprofloxacin elicited a convulsivant effect in presence of fenbufen. Under these experimental conditions, BMY-40062 had no effect on the central nervous system compared to the other tested quinolones in rodents.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Marne La Vallée, France.
authors.forename: C
authors.initials: C
authors.lastname: Guiol
authors.forename: C
authors.initials: C
authors.lastname: Ledoussal
authors.forename: J M
authors.initials: JM
authors.lastname: Surgé
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000037:antagonists & inhibitors; D001831:Body Temperature / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D004347:Drug Interactions; D005260:Female; D024841:Fluoroquinolones; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009287:Naphthyridines / Q000494:pharmacology*; D010433:Pentylenetetrazole; D010654:Phenylbutyrates / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D010654:Phenylbutyrates; C060734:BMY 40062; C010725:fenbufen; D010433:Pentylenetetrazole; D001640:Bicuculline