Anticonvulsant drug actions on in vitro and in vivo levels of cyclic AMP in the mouse brain.

Injections of pentylenetetrazol to mice produced a rise in steady state levels of cyclic AMP in the cerebrum and cerebellum subsequent to sacrifice by focused microwave irradiation. One hour pretreatment with anticonvulsant drugs--phenytoin, phenobarbital, carbamazepine, clonazepam, and diazepam--prevented this pentylenetetrazol-induced rise in cyclic AMP. Anticonvulsant agents which alone depressed steady state levels of cyclic AMP were phenytoin and carbamazepine in the cerebral cortex and carbamazepine in the cerebellum while elevations in the cyclic nucleotide were evoked by clonazepam in the cerebrum and cerebellum or diazepam and phenytoin in the cerebellum. Under in vitro conditions, in which incubated tissue slices of mouse cerebral cortex were used, the stimulation of cyclic AMP by norepinephrine was blocked by carbamazepine greater than phenobarbital greater than phenytoin. Inhibition of adenosine-induced accumulation of cyclic AMP was observed with phenobarbital greater than carbamazepine greater than phenytoin. Clonazepam enhanced this response to adenosine. Ouabain stimulation of cyclic AMP was prevented by carbamazepine, phenytoin greater than clonazepam greater than phenobarbital greater than diazepam. Only the highest concentrations (0.5 mM) of phenytoin, phenobarbital, and carbamazepine reduced the action of KCl on cyclic AMP elevation. Clonazepam and diazepam elevated the basal levels of the cyclic nucleotide.