Halliwell R F, Davey P G, Lambert J J
Department of Pharmacology, School of Health Sciences, University of Sunderland, U.K.
Neuropharmacology. 1995 Dec;34(12):1615-24. doi: 10.1016/0028-3908(95)00106-9.
The neurotoxic effects of 4-quinolones alone and in combination with certain non-steroidal anti-inflammatory drugs (NSAIDs) may be related to an interaction at GABAA and/or ionotropic glutamate receptors. In the present study, the effects of the fluoroquinolone, ciprofloxacin, alone and in combination with the NSAID, biphenyl acetic acid (BPAA), were examined on GABAA-, NMDA-, AMPA-, and kainate-evoked current responses recorded from cultured rat hippocampal neurones, using the whole cell patch clamp technique. GABA-evoked currents were reversibly inhibited by bicuculline (3 microM) and ciprofloxacin (100 microM) to 11 +/- 5 and 38 +/- 7% of control, respectively. BPAA (100 microM) had little affect on the GABA current (the response was 82 +/- 4% of control) but enhanced the inhibitory potency of ciprofloxacin by approx. 3000-fold. The antagonist effects of ciprofloxacin (30 microM) and ciprofloxacin (0.03 microM) together with BPAA (100 microM) on the GABA-evoked current were not voltage-dependent. Whole cell currents evoked by NMDA, AMPA or kainate were little influenced by ciprofloxacin (100 microM), BPAA (100 microM), or ciprofloxacin plus BPAA (both at 100 microM); the responses being > or = 90% of control in all cases. These data suggest that the proconvulsant effects of quinolones when combined with BPAA may be related to antagonism of central GABAA receptors but not to an interaction at ionotropic glutamate receptors.
单独使用4-喹诺酮类药物以及与某些非甾体抗炎药（NSAIDs）联合使用时的神经毒性作用，可能与在GABAA和/或离子型谷氨酸受体上的相互作用有关。在本研究中，采用全细胞膜片钳技术，研究了氟喹诺酮环丙沙星单独使用以及与NSAID联苯乙酸（BPAA）联合使用时，对培养的大鼠海马神经元记录到的GABAA、NMDA、AMPA和海人藻酸诱发的电流反应的影响。荷包牡丹碱（3 microM）和环丙沙星（100 microM）可分别将GABA诱发的电流可逆性抑制至对照的11±5%和38±7%。BPAA（100 microM）对GABA电流影响很小（反应为对照的82±4%），但可使环丙沙星的抑制效力增强约3000倍。环丙沙星（30 microM）和环丙沙星（0.03 microM）与BPAA（100 microM）共同对GABA诱发电流的拮抗作用不依赖电压。NMDA、AMPA或海人藻酸诱发的全细胞电流几乎不受环丙沙星（100 microM）、BPAA（100 microM）或环丙沙星加BPAA（均为100 microM）的影响；在所有情况下，反应均≥对照的90%。这些数据表明，喹诺酮类药物与BPAA联合使用时的促惊厥作用可能与中枢GABAA受体的拮抗作用有关，而与离子型谷氨酸受体的相互作用无关。
