Freed W J
Neuropsychiatry Branch, NIMH Neurosciences Center at Saint Elizabeths, Washington, DC 20032.
Pharmacol Biochem Behav. 1989 Mar;32(3):733-6. doi: 10.1016/0091-3057(89)90026-9.
Impairment of motor coordination by the excitatory amino acid antagonists 2-amino-7-phosphonoheptanoic acid (APH) and glutamic acid diethyl ester (GDEE) was measured and compared to GABA agonists and anticonvulsants and other compounds by the Coughenour inverted screen test. The GABA agonists muscimol and imidazole acetic acid, and the GABA analogue gamma-hydroxybutyric acid were found to produce a marked impairment of motor coordination. The dosages of phenytoin and valproate which impaired motor coordination, on the other hand, were considerably above the dosages which have been reported to inhibit seizures. APH caused motor incoordination at a dosage of 125 mg/kg, and a prolonged motor impairment was present after administration of APH, 250 mg/kg. GDEE did not significantly impair motor coordination in any dosage tested up to 1920 mg/kg. These results further encourage development of more potent GDEE-like compounds as potential anticonvulsants.
通过库格努尔倒屏试验，测定了兴奋性氨基酸拮抗剂2-氨基-7-膦酰庚酸（APH）和谷氨酸二乙酯（GDEE）对运动协调能力的损害，并与γ-氨基丁酸（GABA）激动剂、抗惊厥药及其他化合物进行了比较。发现GABA激动剂蝇蕈醇和咪唑乙酸，以及GABA类似物γ-羟基丁酸会显著损害运动协调能力。另一方面，损害运动协调能力的苯妥英和丙戊酸盐剂量，远高于据报道能抑制癫痫发作的剂量。APH在剂量为125mg/kg时会导致运动不协调，在给予250mg/kg的APH后，会出现长时间的运动功能损害。在高达1920mg/kg的任何测试剂量下，GDEE均未显著损害运动协调能力。这些结果进一步推动了开发更有效的类GDEE化合物作为潜在抗惊厥药的进程。
