Antagonism of Convulsions But Failure to Enhance GABAA Receptor Function by Felbamate in Mice Tolerant to Diazepam：（抽搐,但未能提高GABAA受体拮抗功能通过在老鼠Felbamate宽容安定）.pdfVIP

Neurochemical Research, Vol. 22, No. 6, 1997, pp. 693-697 Antagonism of Convulsions But Failure to Enhance GABAA Receptor Function by Felbamate in Mice Tolerant to Diazepam Mariangela Serra,u Roberta Cuccu,1 Cristina A. Ghiani, M. Giuseppina Pisu,1 Antonella Murgia,1 and Giovanni Biggio1 (Accepted January 24, 1997) The transfer of tolerance between drugs may indicate a common mode of action. The development of cross-tolerance to the anticonvulsant effect of felbamate after long-term treatment of mice with diazepam, a positive modulator of -y-aminobutyric acid (GABA)-mediated transmission, was there- fore studied in order to clarify the mechanism of this action of felbamate . A challenge injection of felbamate, administered 36 h after the last dose of chronic diazepam treatment, antagonized convulsions elicited by administration of isoniazid. In contrast, felbamate had no effect on the isoniazid-induced increase in t-[35S]butylbicyclophosphorothionate binding to cerebral cortical membranes of diazepam-tolerant mice. These results suggest that the action of felbamate on GA- BAergic transmission is not required for the anticonvulsant effect of this drug. This conclusion is consistent with studies that have indicated that the antiepileptic activity of felbamate depends on its modulatory activity at excitatory amino acid receptors.