Dimpfel W, Dalhoff A, Hofmann W, Schlüter G
Pro Science Private Research Institute Gmbh, Linden, Germany.
Eur Neuropsychopharmacol. 1994 Jun;4(2):151-6. doi: 10.1016/0924-977x(94)90009-4.
The excitability of brain matter was tested bt electrically evoked field potentials in the CA1 region of the rat hippocampus in vitro. In contrast to the quinolones which only increased the amplitudes of electrically evoked potentials, aminophylline induced spontaneous firing in the pyramidal cell layer without stimulation in addition to its dose-dependent effects on the amplitudes of the evoked potentials. Threshold doses of the quinolones tested (0.25 microM) increased the amplitudes of evoked potentials in the presence of an otherwise ineffective concentration of aminophylline (0.5 microM) to different degrees, ranging from 135.3% for ciprofloxacin to 223.8% for nalidixic acid. The rank order of potency of CNS side effects reported in the literature correlates very well with the increase of the population spike amplitude in the hippocampus slice preparation. This feature could be important during the development of new chemical analogues of quinolones.
通过体外测定大鼠海马CA1区电诱发场电位来测试脑物质的兴奋性。与仅增加电诱发电位幅度的喹诺酮类药物不同,氨茶碱除了对诱发电位幅度有剂量依赖性影响外,还能在无刺激的情况下诱导锥体细胞层自发放电。所测试的喹诺酮类药物的阈剂量(0.25微摩尔)在氨茶碱(0.5微摩尔)浓度原本无效的情况下,不同程度地增加了诱发电位幅度,环丙沙星增加了135.3%,萘啶酸增加了223.8%。文献中报道的中枢神经系统副作用效力的排序与海马切片制备中群体峰电位幅度的增加非常相关。这一特性在喹诺酮类新化学类似物的研发过程中可能很重要。