The effects of analogues of valproic acid on seizures induced by pentylenetetrazol and GABA content in brain of mice.

The effect of valproic acid and 10 close analogues (7 branched and 3 non-branched) were studied on the content of gamma-aminobutyric acid (GABA) in brain and on seizures induced by pentylenetetrazol (PTZ) in mice. All 8 branched fatty acids protected against seizures induced by pentylenetetrazol, but the 3 non-branched acids were inactive. A significant correlation was observed between side-chain length and anticonvulsant potency. However, sedative and toxic phenomena became apparent with longer chain lengths. The 3 non-branched fatty acids did not alter levels of GABA in brain, but there was a significant correlation between anticonvulsant activity and increased brain GABA levels, for the 8 branched fatty acids. Despite this correlation, one branched analogue, 2-ethylbutyric acid, possessed anticonvulsant activity but did not increase the content of GABA in brain.