Oxcarbazepine does not suppress cortical spreading depression.
BACKGROUND
Cortical spreading depression is the electrophysiological substrate of migraine aura, and may trigger headache. Recently, chronic treatment with five migraine prophylactic drugs was shown to suppress cortical spreading depression, implicating spreading depression as a common therapeutic target in migraine prophylaxis.


METHODS
In order to assess the negative predictive value of spreading depression susceptibility as a preclinical drug screening tool, we tested oxcarbazepine, an anti-epileptic ineffective in migraine prophylaxis. Valproate served as the positive control. Cortical spreading depression susceptibility was measured in rats using topical KCl or electrical stimulation.


RESULTS
Oxcarbazepine did not suppress spreading depression either after a single dose or after daily treatment for 5 weeks. As previously shown, valproate suppressed spreading depression susceptibility after chronic dosing, while a single dose was ineffective.


CONCLUSIONS
These data provide further support for spreading depression as a relevant target in migraine prophylaxis, and demonstrate the predictive utility of employed spreading depression models.
Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Ulrike
U
Hoffmann
Ergin
E
Dileköz
Chiho
C
Kudo
Cenk
C
Ayata
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013181:Cortical Spreading Depression / Q000187:drug effects*; D004558:Electric Stimulation; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology; D000078330:Oxcarbazepine; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D011189:Potassium Chloride; D000078330:Oxcarbazepine