Anticonvulsive activity of several excitatory amino acid antagonists against barbital withdrawal-induced spontaneous convulsions.
Anticonvulsive activity of several excitatory amino acid antagonists against barbital withdrawal-induced spontaneous convulsions.
复制标题
几种兴奋性氨基酸拮抗剂对巴比妥戒断引起的自发性惊厥的抗惊厥活性。
DOI：
10.1016/0014-2999(88)90172-0
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发表时间：
1988
影响因子：
5
通讯作者：
Morgan,WW
中科院分区：
文献类型：
--
作者：
McCaslin,PP;Morgan,WW
对几种兴奋性氨基酸拮抗剂进行了测试，以防止大鼠巴比妥戒断综合征期间出现的自发性惊厥。巴比妥依赖大鼠停用生理盐水、2-氨基-7-膦庚酸(APH)、硫酸镁、谷氨酸二乙酯(GDEE)或顺式-2，3-哌啶二元酸(PDA)后，连续脑室(Icv)注入不影响大鼠正常行为的最大剂量。所有动物在戒断后12~48h连续观察，记录每只动物的自发惊厥次数。此后，用聚焦微波照射处死动物，收集小脑，测定环鸟苷一磷酸(CGMP)水平。APH和硫酸镁均能显著预防惊厥，但只有APH能阻止戒断引起的小脑cGMP升高。PDA和GDEE对小脑cGMP水平和惊厥活动均无统计学意义的影响。尽管GDEE的效果在统计学上不显著，但惊厥次数减少到对照动物的1 3次。这些数据表明，N-甲基-d-天冬氨酸(NMDA)受体介导的癫痫活动与巴比妥类戒断综合征相关，并表明戒断诱导的小脑cGMP升高可以在没有惊厥诱导的情况下发生。
Several excitatory amino acid antagonists were tested for an ability to prevent spontaneous convulsions seen during the barbital abstinence syndrome in rats. Barbital-dependent animals were continuously infused intracerebroventricularly (icv) for the first 48 h following barbital withdrawal with either saline, 2-amino-7-phosphonoheptanoic acid (APH), magnesium sulfate, glutamyldiethyl ester (GDEE) or cis-2, 3-piperidine dicarboxylic acid (PDA) using the highest dosages which did not affect normal behavior of the rats. All animals were observed continuously from 12 to 48 h postwithdrawal and the number of spontaneous convulsions observed in each animal was recorded. After this time, animals were killed by focused microwave irradiaton and the cerebellas were collected for determination of cyclic guanosine monophosphate (cGMP) levels. While both APH and MgSO 4 dramatically prevented convulsions, only APH prevented the withdrawal-induced elevation of cerebellar cGMP. PDA and GDEE had no statistically significant effect on either cerebellar cGMP levels or on convulsive activity. Although the effect of GDEE was not statistically significant, the number of convulsions was reduced to 1 3 those seen in control animals. These data implicate N-methyl-d-aspartate (NMDA) receptor-mediated pathways in seizure activity associated with the barbital abstinence syndrome and show that the withdrawal-induced elevation of cerebellar cGMP can occur without the induction of convulsions.