Fernández, M. et al. Flufenamic acid suppresses epileptiform activity in hippocampus by reducing excitatory synaptic transmission and neuronal excitability. Epilepsia doi:10.1111/j.1528-1167.2009.02279.x

FFA is particularly attractive as it works differently from drugs already approved

Observations in an in vitro model of epilepsy suggest that the NSAID flufenamic acid (FFA) could have therapeutic potential in this condition. FFA suppressed epileptiform activity in a well-established model based on hippocampal slices. “Our data indicate that FFA exerts an anticonvulsant effect by decreasing glutamate excitatory postsynaptic currents and reducing neuronal excitability,” explains senior author Eduardo Martín (University of Castilla-La Mancha, Albacete, Spain).

Previous studies had shown that pretreatment with NSAIDs could attenuate convulsive activity in some animal models, but the cellular and molecular mechanisms involved remain unknown. Miriam Fernández and colleagues demonstrate that FFA damps down abnormal epileptiform activity in the CA1 pyramidal neurons in the hippocampus by mechanisms that are independent of the drug's anti-inflammatory activity. “FFA reduces glutamatergic postsynaptic currents, an action that could explain its antiepileptic effects, since glutamatergic synaptic transmission is known to play a role in epilepsy, and modifies neuronal excitability,” says Martín. He stresses that the two mechanisms are not mutually exclusive and could act synergistically. “This specific regulation would be sufficient to block the cellular and circuital mechanisms that underlie seizure development, so FFA is a good candidate as a refractory epilepsy treatment,” adds Martín.

FFA is particularly attractive as it works differently from drugs already approved. Around 30% of patients with epilepsy fail to respond to current treatments, which substantially erodes their quality of life and contribution to society. “Refractory epilepsy is associated with considerable medical, social and psychiatric complications and enormous financial costs,” notes Martín. He stresses that antiepileptic drugs with novel mechanisms of action “would provide a much-needed boost for epilepsy pharmacotherapy.”

Studies will now be required to confirm the efficacy and safety of FFA in vivo in different animal models, and their suitability for clinical use can only be confirmed by many years of clinical trial. If FFA performs well, future research could also screen other members of the fenamate family—and possibly other NSAIDs—for their therapeutic potential, especially in patients with refractory seizures.