Clonidine Inhibits Interictal-like Epileptiform Events in Prefrontal Cortex Pyramidal Neurons

The mechanism of action of drugs used to treat ADHD has not been fully elucidated. The aim of the study was to assess the effect of clonidine, a drug used to treat ADHD, on interictal-like epileptiform events in prefrontal cortex pyramidal neurons. Epileptiform events (lasting less than 3 s) were recorded in a zero-magnesium and elevated-potassium proepileptic extracellular solution using the patch-clamp methodology. Clonidine 100 µM reduced the frequency of epileptiform events. Moreover, clonidine hyperpolarized the membrane potential recorded in the proepileptic extracellular solution. In the constant presence of the alpha-2 adrenergic receptor antagonist idazoxan 20 µM in all solutions, clonidine 100 µM also inhibited the frequency of interictal-like epileptiform events. This suggests that clonidine inhibited the frequency of interictal events via a direct influence on ionic channels. Furthermore, clonidine inhibited tonic NMDA receptor currents and did not influence tonic AMPA currents. The tested drug inhibited fast-inactivating voltage-gated sodium currents. Blockade of NMDA currents and voltage-gated sodium currents likely contributed to the inhibition of epileptiform events exerted by clonidine. The potential translational relevance of the study is discussed.