Possible interaction of fluoroquinolones with the benzodiazepine-GABAA-receptor complex.
1. The possible involvement of the benzodiazepine (BZD)-GABAA-receptor complex in mediating CNS stimulatory effects of fluoroquinolones was tested in vitro, in a binding inhibition assay and in vivo, in a clinical drug interaction study using electro-encephalogram (EEG) monitoring. 2. The specific binding of [3H]-flunitrazepam to rat synaptic brain membranes was inhibited by various fluoroquinolones in a concentration-dependent manner. 3. Ofloxacin had CNS-stimulating effects as revealed by the EEG which were slightly augmented by flumazenil but reversed by coadministration of midazolam. 4. In conclusion, our findings suggest that clinically observed CNS adverse effects of fluoroquinolones could be mediated at least in part through interaction with the BZD-GABAA-receptor complex and may be controlled by BZD agonist administration.
Unseld
E
E
Dr Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, FRG.
Ziegler
G
G
Gemeinhardt
A
A
Janssen
U
U
Klotz
U
U
D000328:Adult; D000818:Animals; D001923:Brain Chemistry; D002939:Ciprofloxacin / Q000009:adverse effects / Q000494:pharmacology; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D005445:Flunitrazepam / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009643:Norfloxacin / Q000009:adverse effects / Q000494:pharmacology; D015242:Ofloxacin / Q000009:adverse effects / Q000494:pharmacology; D015363:Quinolones / Q000009:adverse effects / Q000494:pharmacology*; D011869:Radioligand Assay; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D015363:Quinolones; D011963:Receptors, GABA-A; D002939:Ciprofloxacin; D005445:Flunitrazepam; D015242:Ofloxacin; D009643:Norfloxacin