Do phenytoin and carbamazepine depress excitation and/or facilitate inhibition?

The effect of phenytoin and carbamazepine on the segmental and the periventricular inhibition was investigated in interneurons of the spinal trigeminal nucleus oralis of cats. The segmental inhibition was elicited by delivering a conditioning stimulus to the maxillary nerve 100 ms prior to the test stimulus to the maxillary nerve, and the periventricular inhibition was elicited by delivering a conditioning stimulus to the periventricular gray matter. Therapeutic serum levels of phenytoin and carbamazepine facilitated the segmental inhibition, but depressed the periventricular inhibition, while also depressing the response of trigeminal nucleus neurons to an unconditioned maxillary nerve stimulus. These results indicate that the depression of neural activity by phenytoin and carbamazepine is selective, leaving some inhibitory pathways relatively untouched and thus greatly enhancing their effectiveness. It is suggested that the anticonvulsant properties of phenytoin and carbamazepine are due to their ability to produce a relative facilitation of inhibitory feedback mechanisms.