Effects of quinolone carboxylic acid derivatives on GABAA receptor-mediated stimulation of gastric acid secretion and intestinal motility.
The present study investigates the effects of some quinolone carboxylic acid derivatives on GABAA 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 acetylcholine. Taken together, these results suggest that the quinolone derivatives tested act as antagonists at both central and peripheral GABAA receptors. In addition, GABAA-mediated gastrointestinal responses might represent a simple and reliable method to assay the GABAA receptor antagonist properties of new quinolone derivatives.
Blandizzi
C
C
Institute of Medical Pharmacology, University of Pisa, Italy.
De Bona
M
M
Natale
G
G
Agen
C
C
Del Tacca
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009268:Nalidixic Acid / Q000494:pharmacology*; D009643:Norfloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D010876:Pipemidic Acid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects
D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D009118:Muscimol; D009268:Nalidixic Acid; D003847:Deoxyglucose; D010876:Pipemidic Acid; D009643:Norfloxacin; D000109:Acetylcholine