78435-49-1Relevant academic research and scientific papers
Examining the correlations between GSK-3 inhibitory properties and anti-convulsant efficacy of valproate and valproate-related compounds
Werstuck, Geoff H.,Kim, Anna J.,Brenstrum, Timothy,Ohnmacht, Stephan A.,Panna, Ella,Capretta, Alfredo
, p. 5465 - 5467 (2004)
A family of compounds based upon the chemical structure of valproate were synthesized and assayed for their ability to inhibit glycogen synthase kinase (GSK)-3 α and β activity in vitro. A family of compounds based upon the chemical structure of valproate were synthesized and assayed for their ability to inhibit glycogen synthase kinase (GSK)-3 α and β activity in vitro. This data is correlated to the known anti-convulsant properties of these compounds in order to determine the potential role of GSK-3 inhibition in the therapeutic efficacy of these drugs.
Structure-activity relationships of unsaturated analogues of valproic acid
Palaty,Abbott
, p. 3398 - 3406 (2007/10/02)
The principal metabolite of valproic acid (VPA), 2-ene VPA, appears to share most of VPA's pharmacological and therapeutic properties while lacking its hepatotoxicity and teratogenicity, thus making it a useful lead compound for the development of safer antiepileptic drugs. Analogues of 2-ene VPA were evaluated for anticonvulsant activity in mice using the subcutaneous pentylenetetrazole test. Cyclooctylideneacetic acid exhibited a potency markedly exceeding that of VPA itself with only modest levels of sedation. Potency, as either ED50 or brain concentration, was highly correlated (r > 0.85) with volume and lipophilicity rather than with one of the shape parameters calculated by molecular modeling techniques, arguing against the existence of a specific receptor site. Instead, a role for the plasma membrane in mediating the anticonvulsant effect is suggested.
