Abstract
The present study investigates the effects of some quinolone carboxylic acid derivatives on GABA A receptor-mediated excitatory responses in gastrointestinal preparations in vivo and in vitro. In stomach-perfused rats, norfloxacin, nalidixic and pipemidic acid dose dependently antagonized acid hypersecretion induced by muscimol. Under the same conditions, the quinolone derivatives failed to modify acid hypersecretion evoked by 2-deoxy-D-glucose. In the isolated guinea-pig ileum, norfloxacin, nalidixic and pipemidic acid antagonized muscimol-elicited contractions in a non-competitive manner. In contrast, these drugs did not influence ileal cholinergic contractions evoked by transmural electrical stimulation or by exogenous acctylcholine. Taken together, these results suggest that the quinolone derivatives tested act as antagonists at both central and peripheral GABA A receptors. In addition, GABA A-mediated gastrointestinal responses might represent a simple and reliable method to assay the GABA A receptor antagonist properties of new quinolone derivatives.
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