Impaired motor coordination in mice induced by 2-amino-7-phosphonoheptanoic acid (APH), glutamic acid diethyl ester (GDEE), and other compounds

Abstract

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.