PT  - JOURNAL ARTICLE
AU  - W. D. LUST
AU  - H. J. KUPFERBERG
AU  - W. D. YONEKAWA
AU  - J. K. PENRY
AU  - J. V. PASSONNEAU
AU  - A. B. WHEATON
TI  - Changes in Brain Metabolites Induced by Convulsants or Electroshock: Effects of Anticonvulsant Agents
DP  - 1978 Mar 01
TA  - Molecular Pharmacology
PG  - 347--356
VI  - 14
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/14/2/347.short
4100  - http://molpharm.aspetjournals.org/content/14/2/347.full
SO  - Mol Pharmacol1978 Mar 01; 14
AB  - In general, cyclic 3',5'-GMP concentrations in the cerebellum are elevated by convulsants and diminished by anticonvulsant agents, whereas the levels of cyclic 3',5'-AMP remain unchanged by either treatment. Furthermore, the effect of convulsants on cerebellar cyclic GMP is antagonized by anticonvulsants, and the anticonvulsant activity persists concurrently with the biochemical changes. Maximal electroshock (MES) causes an elevation of cerebellar cyclic AMP during the excitable phase. It is suggested that the elevation of cyclic AMP is inhibitory to the Punkinje cell output and thus favors the seizure state. Phenytoin suppresses the increase in cerebellar cyclic AMP, which would reduce seizure activity. Phenytoin also prevents other metabolic changes induced by MES in the cerebellum, but not the cerebral cortex, indicating that these effects are not simply prevention of anoxia. It is proposed that phenytoin has a locus of action that attenuates the electroshock signal to the cerebellum or suppresses the response by a direct effect on the metabolic machinery.