Gupta P, Khobragade S B, Shingatgeri V M
Central Research Institute for Homoeopathy, A-1/1, Sec-24, Noida-201 301, India.
Drug Safety Evaluation, Ranbaxy Research Laboratories, Plot No. 20, Sector 18, Gurgaon-122 015, India.
Indian J Pharm Sci. 2014 Mar;76(2):157-63.
Recently zebrafish larvae have emerged as a high-throughput model for screening pharmacological activities. The present study was undertaken to investigate the effect of established anticonvulsants, such as valproic acid, carbamazepine, gabapentin, diazepam, lacosamide and pregabalin against pentylenetetrazole (6 mM) seizures in adult zebrafish. Different phases of seizures (increase swim activity, rapid whirlpool-like circling swim behaviour and brief clonus-like seizures leading to loss of posture) were elicited in zebrafish on exposure for 15 min to 6 mM pentylenetetrazole. The exposure of zebrafish to an increasing concentration of the anticonvulsants alongside 6 mM pentylenetetrazole showed concentration-dependent elevation of seizure latency against pentylenetetrazole-induced seizures except for pregabalin, which failed to produce any anticonvulsant activity in zebrafish. Moreover the proconvulsant activity of caffeine was also evaluated using suboptimal concentration (4 mM) of pentylenetetrazole in adult zebrafish. Decrease in seizure latency of different phases of seizures was observed with increasing concentration of caffeine compared with its respective control group. In view of the above findings, the results of the present study suggested that adult zebrafish produce the expected anticonvulsive and proconvulsive effects and could potentially be used as a screen in future epilepsy research.
最近，斑马鱼幼体已成为一种用于筛选药理活性的高通量模型。本研究旨在调查已确定的抗惊厥药物，如丙戊酸、卡马西平、加巴喷丁、地西泮、拉科酰胺和普瑞巴林对成年斑马鱼戊四氮（6 mM）诱导的癫痫发作的影响。在成年斑马鱼暴露于6 mM戊四氮15分钟后，引发了癫痫发作的不同阶段（游泳活动增加、快速漩涡状转圈游泳行为以及导致姿势丧失的短暂阵挛样癫痫发作）。将斑马鱼暴露于浓度不断增加的抗惊厥药物与6 mM戊四氮中，结果显示，除普瑞巴林外，其他药物对戊四氮诱导的癫痫发作的癫痫发作潜伏期呈浓度依赖性延长，普瑞巴林在斑马鱼中未产生任何抗惊厥活性。此外，还使用亚最佳浓度（4 mM）的戊四氮在成年斑马鱼中评估了咖啡因的促惊厥活性。与各自的对照组相比，随着咖啡因浓度的增加，观察到癫痫发作不同阶段的癫痫发作潜伏期缩短。鉴于上述发现，本研究结果表明成年斑马鱼产生了预期的抗惊厥和促惊厥作用，并且有可能在未来的癫痫研究中用作筛选模型。
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