Aim: 

Valproic acid (VPA) is one of four first-line antiepileptic drugs (AEDs) established in the treatment of epilepsy. With the aim to improve pharmacokinetic properties, enhance brain penetration and anticonvulsant potency, avoid side effects, we synthesized and characterized a new molecule, N-Valproil-L-Tryptophan (VPA-TRP). Using extracellular field potential measurements, we compared the effects of VPA and VPA-TRP on the experimental in vitro model of epileptiform activity, named Seizure-Like Events (SLE), in rat brain slices.

Methods: 

Rat brain slices were placed in an interface holding chamber continuously perfused with oxygenated artificial cerebrospinal fluid (aCSF). Epileptiform activity was induced by increasing K⁺ and lowering Ca²⁺ and Mg²⁺ concentration in aCSF. Extracellular field potential recordings were performed and data were stored and analyzed. The drugs were added to modified aCSF and pharmacological treatment parameters were statistically analyzed.

Results: 

Both drugs reversibly reduced the epileptiform activity. VPA-TRP appeared to be more effective than VPA treatment also using lower concentration. VPA-TRP reversibly blocked the paroxystic discharges of single neuron too.

Conclusion: 

VPA-TRP was slightly more effective than VPA itself. If VPA-TRP stands the toxicological tests, it might be a useful alternative in the treatment of seizures.