Czuczwar S J, Turski L, Schwarz M, Turski W A, Kleinrok Z
Eur J Pharmacol. 1984 May 4;100(3-4):357-62. doi: 10.1016/0014-2999(84)90013-x.
The effects of L-glutamic acid diethyl ester (GDEE), D,L-alpha-aminoadipic acid (alpha-AA) and D,L-2-aminophosphonovaleric acid (APV) on the anticonvulsant action of phenobarbital and of diphenylhydantoin were studied in mice against electroconvulsions. Anticonvulsants were administered intraperitoneally 60 min and amino-acid antagonists 30 min before the test, by the same route. Neither GDEE (up to 400 mg/kg) nor alpha-AA (up to 100 mg/kg) were found to affect the seizure threshold whilst APV (100 and 200 mg/kg) raised the threshold moderately from 6.2 to 8.4 and 9.0 mA. APV and alpha-AA (up to 100 mg/kg) and GDEE (up to 400 mg/kg) did not affect the anticonvulsant potency of diphenylhydantoin. Only APV in the dose of 200 mg/kg potentiated the protective efficacy of this antiepileptic against maximal electroshock to a relatively low degree. The anticonvulsant action of phenobarbital was enhanced by APV (25-200 mg/kg) and alpha-AA in the dose of 50 but not in the dose of 100 mg/kg, GDEE being completely ineffective. These results suggest that the blockade of N-methyl-D-aspartic acid receptors by alpha-AA and APV is mainly responsible for the potentiation of the anticonvulsant activity of phenobarbital. The anticonvulsant effects of both antiepileptics do not seem to be related to the suppression by GDEE of events mediated by receptors for quisqualic acid.
在小鼠身上研究了L-谷氨酸二乙酯（GDEE）、D，L-α-氨基己二酸（α-AA）和D，L-2-氨基膦酰基戊酸（APV）对苯巴比妥和苯妥英抗惊厥作用的影响，以对抗电惊厥。抗惊厥药在测试前60分钟腹腔注射，氨基酸拮抗剂在测试前30分钟通过相同途径腹腔注射。未发现GDEE（高达400mg/kg）和α-AA（高达100mg/kg）影响惊厥阈值，而APV（100和200mg/kg）可将阈值从6.2mA适度提高到8.4mA和9.0mA。APV、α-AA（高达100mg/kg）和GDEE（高达400mg/kg）不影响苯妥英的抗惊厥效力。仅200mg/kg剂量的APV可将这种抗癫痫药对最大电击的保护效力增强到相对较低的程度。APV（25 - 200mg/kg）和50mg/kg剂量的α-AA可增强苯巴比妥的抗惊厥作用，而100mg/kg剂量的α-AA则无效，GDEE完全无效。这些结果表明，α-AA和APV对N-甲基-D-天冬氨酸受体的阻断主要是苯巴比妥抗惊厥活性增强的原因。两种抗癫痫药的抗惊厥作用似乎与GDEE对喹啉酸受体介导的事件的抑制无关。
