Ben Bassat I, Bitterman N
Israeli Naval Hyperbaric Institute, Haifa.
Eur J Pharmacol. 1993 Apr 1;228(5-6):241-6. doi: 10.1016/0926-6917(93)90056-v.
The toxicity of hyperbaric oxygen in the central nervous system is expressed by generalized tonic-clonic seizures. In the search for drugs effective against these seizures, we tested flunarizine, a calcium antagonist known to have antiepileptic properties and only minimal cardiovascular side effects. 49 rats with chronic cortical electrodes were injected i.p. with six different doses of flunarizine (10-300 mg/kg) or vehicle, before exposure to 0.5 MPa oxygen. Two doses of flunarizine and vehicle were given to rats exposed to oxygen with 5% CO2 at an absolute pressure of 0.5 MPa. EEG and spectral analysis of background EEG activity were monitored. The duration of the latent period before the appearance of electrical discharges in the EEG was used as an index of oxygen toxicity. There was no statistical difference between the duration of the latent periods for the seven groups treated by flunarizine or by vehicle on exposure to 0.5 MPa pure oxygen (P = 0.9 in ANOVA), but on exposure to oxygen with CO2, there was significant prolongation of the latent periods in comparison with vehicle (P < 0.001). Our results suggest that on exposure to hyperbaric oxygen, the antiepileptic effect of flunarizine might be masked, probably by its cerebral antivasoconstrictive effect.
高压氧对中枢神经系统的毒性表现为全身性强直阵挛性癫痫发作。在寻找有效对抗这些癫痫发作的药物时，我们测试了氟桂利嗪，一种已知具有抗癫痫特性且仅有极小心血管副作用的钙拮抗剂。49只植入慢性皮层电极的大鼠在暴露于0.5MPa氧气之前，经腹腔注射六种不同剂量的氟桂利嗪（10 - 300mg/kg）或赋形剂。将两种剂量的氟桂利嗪和赋形剂给予在绝对压力为0.5MPa且含有5%二氧化碳的氧气环境中暴露的大鼠。监测脑电图（EEG）及背景EEG活动的频谱分析。EEG中放电出现前潜伏期的持续时间被用作氧毒性的指标。在暴露于0.5MPa纯氧时，氟桂利嗪处理组和赋形剂处理组的七组大鼠潜伏期持续时间之间无统计学差异（方差分析中P = 0.9），但在暴露于含二氧化碳的氧气时，与赋形剂相比潜伏期显著延长（P < 0.001）。我们的结果表明，在暴露于高压氧时，氟桂利嗪的抗癫痫作用可能被掩盖，可能是由于其脑内抗血管收缩作用。
