Continuously infused 2-amino-7-phosphonoheptanoic acid antagonizes N-methyl- d-aspartate-induced elevations of cyclic GMP in vivo in multiple brain areas and chemically-induced seizure activity

Abstract

The effects of the chronic intracerebroventricular (i.c.v.) infusion of the potent dicarboxylic amino acid antagonist, 2-amino-7-phosphonoheptanoic acid (APH), were examined in female rats as a prelude to the use of this compound in exploring the role of dicarboxylic amino acids in barbiturate dependence and withdrawal. Doses of APH ranging from 2.7 to 54 μg/day were examined for signs of toxicity. Weight loss, decreased water intake and locomotor impairment were found only with the largest dose. No significant changes in consumption of food or body temperature were observed with any dose. The chronic administration of the drug (27 μg/day) blocked the elevation of the content of cyclic guanosine monophosphate induced by N-methyl- d-aspartate (NMDA) in all regions of the brain examined. The chronically-administered drug also blocked wild running behavior induced by the intracerebroventricular administration of two different drugs n-methyl- d-aspartic add and cyclohexylbarbiturate add. However, APH was ineffective in suppressing convulsions induced by the ED 50 dose of pentylenetetrazol given subcutaneously.