Biphenylacetic acid enhances the antagonistic action of fluoroquinolones on the gabaA-mediated responses of the isolated guinea-pig ileum

Abstract This paper examines the effect of biphenylacetic acid on the antagonistic action of norfloxacin and enoxacin on the GABA A -mediated responses of the isolated guinea-pig ileum. GABA produced transient contractions followed by relaxation. The contractile effect of exogenously applied GABA was concentration-dependent with EC 5 0 = 9.8 × 10 − 6 M. This contractile effect was not significantly modified by biphenylacetic acid, and the EC 5 0 value for GABA in the presence of 10 − 5 M biphenylacetic acid was 1.15 × 10 − 5 M. The GABA contractile effect was inhibited, dose-dependently, by either norfloxacin or enoxacin, but only at concentrations higher than 10 − 5 M. The response of the ileum to GABA (at EC 5 0 ) was reduced to 35 and 36% by pretreatment with 10 − 5 M norfloxacin or enoxacin, respectively. However, in the presence of 10 − 5 M biphenylacetic acid, the response of the ileum to GABA was reduced to 2.2% by pretreatment with 10 − 5 M enoxacin, while it was completely abolished by pretreatment with 10 − 5 M norfloxacin and the IC 5 0 values were 5.5 × 10 − 7 and 1.5 × 10 − 6 M for norfloxacin and enoxacin, respectively. These data show that biphenylacetic acid whilst having no effect at the GABA A -mediated contractile response of the guinea-pig ileum, enhances the antagonistic effect of both enoxacin and norfloxacin. This suggests that combined administration of fluoroquinolones and biphenylacetic acid synergistically inhibits GABA A -receptors at the intestinal level.