Valproate and 4-methyloctanoic acid, an analogue of valproate, in animal models of epilepsy

摘要: Valproic acid (VPA) is a commonly used drug for the treatment of epilepsy, bipolar disorder and migraine, yet its mechanisms action are unknown. The neuroprotective effect VPA has been hypothesized to be secondary inhibition cAMP/protein kinase A (PKA) pathway. Here, result show that (1mM) inhibited mossy fibre long-term potentiation induced (LTP) by application high frequency stimulation in dentate gyrus. Furthermore, enhancement fibre responses forskolin (50 μM), consistent with an effect on the PKA Using biochemical assays, it was further demonstrated this not due direct PKA, but resulted from adenylyl cyclase. The results using in vitro seizure models (Pentylenetetrazole model low- Mg2+ model) mechanism cannot fully explain VPA’s anti-seizure effect, but rather, modifying synaptic plasticity, may more important VPA’s antiepileptogenic neuroprotective action. therefore distinct of action contribute diverse biological activity. In hippocampi epileptic rats (following pilocarpine-induced status epilepticus), not control tissue, affects short-term indicating have specific effects rather than animals. Using low-Mg2+ in vivo epilepticus (the perforant pathway model), 4- methyloctanoic established potent antiepileptic than VPA provides which similar VPA. fibre responses by application 4-methyloctanoic shares same effect as modulation PKA.