Valproic Acid (VPA) is used alone or with other medications to treat certain types of seizures such as epileptic seizures. It is also used to prevent migraine headaches and to treat mania (episodes of frenzied, abnormally excited mood) in people with bipolar disorder. However, the clinical use of VPA is limited due to severe side-effects of tetratogenicity and hepatotoxicity.
As a small branched fatty acid having a wide range of CNS activity, VPA is a good target for structure modification studies. This is why there have been many attempts to find a superior compound that is similar to VPA, with broad spectrum activity and an improved side effect profile.
Prof. Bialer has developed a novel VPA derivative – sec-Butylpropylacetamide (SPD). Pre-clinical studies have shown that the new compound possess a unique and broad-spectrum anti-seizure profile, superior to that of VPA. SPD blocked behavioral and electrographic status epilepticus (SE) induced by pilocarpine and the organophosphates soman and paraoxon. Moreover SPD did not cause the side-effects of VPA in mice models.
SPD is a novel valproic acid derivative that may be used as a potential treatment for a variety of CNS disorders, which currently have unmet needs, like epilepticus in which approximately 40% of the patients will continue to experience breakthrough seizures despite stable antiepileptic drug regimens. The main advantage of SPD is its safety profile compared to VPA.
The activity spectrum of SPD related to CNS disorders includes epileptic seizures, pain and also a countermeasure for nerve agent seizures.