Carbamazepine and phenytoin inhibit somatostatin release from dispersed cerebral cells in culture.
To elucidate the mechanism by which carbamazepine lowers somatostatin concentration in cerebrospinal fluid of humans, the effect of carbamazepine on secretion of this peptide was studied in rat cerebral cell cultures. Concentrations of carbamazepine within the therapeutic range (4 x 10(-5) M) inhibited spontaneous release of somatostatin and blocked secretory responses to the epileptogen, picrotoxin, and to the cyclic cAMP stimulator forskolin. One of the proposed mechanisms of carbamazepine action is that it binds to adenosine receptors, but in this study, aminophylline, an adenosine antagonist, in a concentration as high as 2.4 x 10(-4) M, did not reverse carbamazepine effects. Carbamazepine suppression of picrotoxin, however, was overcome by exposure to veratridine, a sodium channel-active compound. This finding supports the hypothesis that carbamazepine acts by binding to sodium channels. Phenytoin, another anticonvulsant with many similar properties, also blocked picrotoxin-induced somatostatin release at a concentration of 10(-4) M, and its effects were also reversed by veratridine at a concentration of 10(-5) M. These findings clarify the mechanism by which carbamazepine and phenytoin act in epilepsy and trigeminal neuralgia.
Reichlin
S
S
Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111.
Mothon
S
S
D000818:Animals; D002220:Carbamazepine / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D013004:Somatostatin / Q000378:metabolism*
D002220:Carbamazepine; D005576:Colforsin; D010672:Phenytoin; D010852:Picrotoxin; D011983:Receptors, Purinergic; D015222:Sodium Channels; D013004:Somatostatin