From the Research
Ezogabine is a potassium channel opener that works primarily by activating voltage-gated potassium channels in neurons, specifically the KCNQ (Kv7) channels, which is described in option A. The mechanism of action of ezogabine involves the activation of KCNQ channels, particularly subtypes KCNQ2-5 (Kv7.2-7.5), leading to an increase in the M-current, a neuronal potassium current that helps stabilize the resting membrane potential and control neuronal excitability 1. When ezogabine binds to KCNQ channels, it causes them to open more readily at less depolarized membrane potentials, resulting in an enhanced potassium efflux from neurons, which hyperpolarizes the cell membrane, making it more difficult for neurons to reach the threshold potential required to generate action potentials 2. By reducing neuronal excitability in this way, ezogabine decreases the likelihood of abnormal, synchronized firing patterns that characterize seizures, which is the primary mechanism by which it exerts its anticonvulsant effects 3. The typical dosing of ezogabine ranged from 600-1200 mg daily, divided into three doses, although it has been withdrawn from the market due to side effects including retinal pigmentation changes and blue skin discoloration with long-term use 4. Key points about ezogabine's mechanism of action include:
- Activation of KCNQ (Kv7) channels
- Increase in the M-current
- Hyperpolarization of the cell membrane
- Reduction of neuronal excitability
- Decrease in the likelihood of abnormal, synchronized firing patterns that characterize seizures
- Typical dosing: 600-1200 mg daily, divided into three doses 5.