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

## TL;DR

Clonidine, a drug for ADHD, reduces seizure-like activity in prefrontal cortex neurons, possibly by affecting ion channels and NMDA receptors.

## Contribution

This study demonstrates that clonidine inhibits epileptiform events via direct modulation of ionic channels and NMDA receptors.

## Key findings

- Clonidine 100 µM reduced the frequency of interictal-like epileptiform events in prefrontal cortex neurons.
- Clonidine inhibited tonic NMDA receptor currents and fast-inactivating voltage-gated sodium currents.
- The effect of clonidine was not blocked by an alpha-2 adrenergic receptor antagonist, suggesting a direct channel influence.

## Abstract

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.