Urbańska E M, Drelewska E, Borowicz K K, Błaszczak P, Kleinrok Z, Czuczwar S J
Department of Pharmacology and Toxicology, Medical University School, Lublin, Poland.
J Neural Transm (Vienna). 1996;103(10):1145-52. doi: 10.1007/BF01271199.
Nitric oxide may be involved in seizure phenomena even though data often seem to be contradictory. This prompted us to study the influence of nitric oxide upon electrically and chemically induced seizures. The effects of nitric oxide synthase inhibitor, NG-nitro-L-arginine (NNA), on pentylenetetrazol-, aminooxyacetic acid-, aminophylline-induced seizures or electroconvulsive shock were evaluated. NNA was applied at 1, 10 and 40 mg/ kg 0.5 and 2.0 h before chemical seizures and at 1 and 40 mg/kg 0.5 and 2.0 h prior to electroconvulsions. The nitric oxide synthase inhibitor (up to 40 mg/ kg) did not affect the susceptibility of mice to pentylenetetrazol, amino-oxyacetic acid or electroconvulsions. However, NNA significantly enhanced the convulsive properties of aminophylline when applied at 40 mg/kg, 0.5 h before the test. The CD50 value for aminophylline-induced clonus and tonus/ mortality was decreased from 233 to 191 and from 242 to 212 mg/kg, respectively. However, this pretreatment also led to a significant increase in the plasma levels of theophylline. Our results suggest that differential effects of NNA on chemically-induced convulsions might in some cases be associated with a pharmacokinetic interaction.
尽管数据常常看似相互矛盾，但一氧化氮可能与癫痫发作现象有关。这促使我们研究一氧化氮对电诱导和化学诱导癫痫发作的影响。评估了一氧化氮合酶抑制剂NG-硝基-L-精氨酸（NNA）对戊四氮、氨氧基乙酸、氨茶碱诱导的癫痫发作或电惊厥休克的作用。在化学诱导癫痫发作前0.5小时和2.0小时，以及在电惊厥前0.5小时和2.0小时，分别以1、10和40mg/kg的剂量施用NNA。一氧化氮合酶抑制剂（高达40mg/kg）不影响小鼠对戊四氮、氨氧基乙酸或电惊厥的易感性。然而，在试验前0.5小时以40mg/kg的剂量施用NNA时，NNA显著增强了氨茶碱的惊厥特性。氨茶碱诱导的阵挛和强直性发作/死亡率的半数惊厥剂量值分别从233mg/kg降至191mg/kg，从242mg/kg降至212mg/kg。然而，这种预处理也导致茶碱的血浆水平显著升高。我们的结果表明，NNA对化学诱导惊厥的不同作用在某些情况下可能与药代动力学相互作用有关。
