Convulsive activity of alpha-guanidinoglutaric acid and the possible involvement of 5-hydroxytryptamine in the alpha-guanidinoglutaric acid-induced seizure mechanism.

alpha-Guanidinoglutaric acid (alpha-GGA) was first found in cobalt-induced epileptogenic focus tissue in the cerebral cortex of cats. We examined the effect of alpha-GGA on the electroencephalogram and on the brain 5-hydroxytryptamine (5-HT) level after intraventricular administration into rats. Sporadic low-voltage spikes appeared 4 min after the administration of alpha-GGA. Spikes increased in voltage 6 min after the administration. Multiple spikes appeared 10 min after the administration, and they reached maximal frequency 30 min after the administration. The epileptic discharges disappeared 100 min after the administration. The 5-HT level increased in the right and left cortices 3 min after the administration. The 5-HT level decreased in the mid-brain 5 min after the administration and subsequently in all regions of the brain 10 min after the administration. No change in the 5-HT level was found 30 min and 100 min after the administration. These results show that alpha-GGA induces epileptic seizures in rats after intraventricular administration. The results also suggest that alpha-GGA-induced seizures are associated with abnormal serotonergic function and that they are initiated by a decrease in the 5-HT level.