Acute anticonvulsant activity of structural analogues of valproic acid and changes in brain GABA and aspartate content.
Ten analogues of valproic acid (substituted butyric, pentanoic and hexanoic acids) were tested for anticonvulsant activity against audiogenic seizures in DBA/2 mice. There is a consistent correlation between the structure of these branched-chain fatty acids and their anticonvulsant potency, the larger molecules being the more active. There is also a strong correlation between the anticonvulsant potency of these compounds and their ability to reduce cerebral aspartate levels. Cerebral GABA levels are elevated by most, but not all, of the actively anticonvulsant valproate analogues.
D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001224:Aspartic Acid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008811:Mice, Inbred DBA; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014635:Valproic Acid / Q000031:analogs & derivatives*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid