Swedberg M D, Jacobsen P, Honoré T
Novo Nordisk, Pharmaceuticals Division, Malov, Denmark.
J Pharmacol Exp Ther. 1995 Sep;274(3):1113-21.
The anticonvulsant effects of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), phencyclidine (PCP) and diazepam against audiogenic seizures in DBA/2 mice and against seizures induced by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in NMRI mice were compared. Motor impairment was assessed in a rotarod apparatus in DBA/2 as well as NMRI mice. At 30 min after i.p. administration, NBQX was as effective as PCP and diazepam in protecting against audiogenic seizures and had a therapeutic ratio slightly higher than diazepam's and 7-fold higher than PCP's. Whereas diazepam was fully effective, NBQX and PCP were both ineffective against seizures induced by DMCM 30 min after i.p. administration. The anticonvulsant potential and motor-impairing effects of NBQX were evaluated further by the i.p. and the i.v. routes at different time points after administration. At all pretreatment intervals, NBQX protected against audiogenic seizures more potently than it produced motor impairment. NBQX administered i.p. protected against DMCM-induced seizures when given 15 min but not 5 min before testing, whereas after i.v. administration NBQX produced anticonvulsant and motor-impairing effects in the same dose range. NBQX only slightly and non-dose-dependently attenuated the discriminative effects of pentylenetetrazole in rats, showing a limited anxiolytic potential. NBQX produced no PCP-like or morphine-like discriminative effects in rats, suggesting lack of PCP or opiate-like subjective effects. These data demonstrate that NBQX has anticonvulsant effects, has limited anxiolytic effects, and does not produce subjective effects of PCP or opiate type.
比较了2,3 - 二羟基 - 6 - 硝基 - 7 - 氨磺酰基 - 苯并(f)喹喔啉（NBQX）、苯环利定（PCP）和地西泮对DBA/2小鼠听源性惊厥以及对NMRI小鼠由甲基 - 6,7 - 二甲氧基 - 4 - 乙基 - β - 咔啉 - 3 - 羧酸酯（DMCM）诱导的惊厥的抗惊厥作用。在DBA/2小鼠和NMRI小鼠的转棒试验中评估运动功能损害。腹腔注射给药30分钟后，NBQX在预防听源性惊厥方面与PCP和地西泮效果相当，其治疗指数略高于地西泮，比PCP高7倍。虽然地西泮完全有效，但腹腔注射给药30分钟后，NBQX和PCP对DMCM诱导的惊厥均无效。通过腹腔注射和静脉注射途径在给药后的不同时间点进一步评估了NBQX的抗惊厥潜力和运动损害作用。在所有预处理间隔中，NBQX预防听源性惊厥的效力比其产生运动损害的效力更强。腹腔注射的NBQX在测试前15分钟给药时可预防DMCM诱导的惊厥，但在5分钟前给药则无效，而静脉注射给药后，NBQX在相同剂量范围内产生抗惊厥和运动损害作用。NBQX仅轻微且非剂量依赖性地减弱戊四氮在大鼠中的辨别效应，显示出有限的抗焦虑潜力。NBQX在大鼠中未产生类似PCP或吗啡的辨别效应，表明缺乏PCP或阿片样主观效应。这些数据表明，NBQX具有抗惊厥作用，抗焦虑作用有限，且不产生PCP或阿片类主观效应。
