Anticonvulsant activity of 4,9-dioxo-5,10-diazatetradecane (CM 40142), a new GABA derivative, in mice and photosensitive baboons).

The authors describe the anticonvulsant activity of a new gamma-amino-butyric acid (GABA) derivative in several animal models of generalized epilepsy including photoepileptic baboons. In all the studies, 4,9-dioxo-5,10-diazatetradecane (CM 40 142) revealed potencies against chemically, electrically and photic-induced seizures very similar to those observed with sodium valproate. In chemically elicited seizures in mice, CM 40142 exhibited a higher potency than sodium valproate in antagonizing anti-GABAergic agents. Although CM 40142 was synthesized as a compound which would cross the blood-brain barrier and liberate GABA within the central nervous system, preliminary biochemical investigations in mice failed to demonstrate a rise in brain GABA levels after treatment with CM 40142. Furthermore, CM 40142 increased spontaneous motility in mice at anticonvulsant doses. The data suggest that CM 40142 could be a broad spectrum nonsedative antiepileptic agent.