The proconvulsive activity of quinolone antibiotics in an animal model.
The side-effect profile of quinolone antibiotics in man includes CNS disturbances such as dizziness, insomnia and convulsions. Although it has been suggested that the proconvulsive liability of quinolones involves an interaction with GABA receptors in the central nervous system, no animal model has been described to evaluate or confirm the mechanism of this effect. The proconvulsive activity of the quinolone antibiotics, nalidixic (NAL) and oxolinic (OXO) acid were tested in male mice following oral doses of 10-100 mg/kg utilizing the convulsive stimuli pentylenetetrazole (PTZ), picrotoxin, strychnine or electroshock. While NAL and OXO did not alter the threshold for convulsions induced by PTZ, strychnine or picrotoxin, both agents lowered the threshold for electroshock-induced seizures. Furthermore, the proconvulsive actions of NAL and OXO were completely blocked by the excitatory amino acid receptor antagonists, MK-801 and 2-amino-4-phosphonobutyric acid (AP-4). These data indicate that the mechanism of convulsive liability of quinolone antibiotics does not involve GABA receptor interactions as previously thought, but appears to involve activation of excitatory amino acid (EAA) receptors, possibly located in the optic region of the central nervous system.
Williams
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Toxicology Division, Lilly Research Laboratories, Greenfield, IN 46140.
Helton
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DR
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009268:Nalidixic Acid / Q000633:toxicity*; D010093:Oxolinic Acid / Q000633:toxicity*; D010433:Pentylenetetrazole / Q000633:toxicity; D010852:Picrotoxin / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013331:Strychnine / Q000633:toxicity
D000890:Anti-Infective Agents; D003292:Convulsants; D009268:Nalidixic Acid; D010093:Oxolinic Acid; D010433:Pentylenetetrazole; D010852:Picrotoxin; D013331:Strychnine