Sorry I am going to be a bit technical here, but it may interest some of you.
Potassium channel modulators should not be compared, there is a ton of parameters and subtilities that can change drastically the impact of one drug.
Flupirtine acts mainly on the Kv7.3 , retigabine specifically acts on the neuronally expressed KCNQ2-KCNQ5 (Kv7.2-Kv7.5) channels, AUT00063 will act on the Kv3 channels.
Talking from a neuronal perspective, Kv7 and Kv3 mediate the channels and more precisely the action potential.
The action potential is an electrical signal generated near the cell body of a neuron that propagates along the axon to the axon terminals.
After an acoustic trauma, or after taking some drugs such as quinine there is an interference with the excitability of spiral ganglion neurons (The evil glutamate is guilty). The membrane potential changes and the modification of the action-potential waveform induced by the problem put the individual in a T. state.
Going back to the potassium channels, Kv7 channels primarily control the interspike interval with a limited effect of the repolarization. Kv3 channels control the repolarization of the action potential and are expected to induce a new state.
The idea is to open the right channels to lead to a neuronal hyperpolarization, thereby stabilizing the membrane potential and decreasing excitability.(No or very little Tinnitus)
Conclusions:
- Despite a drug being potassium channel openers, it has to be very precise to work.
- Flupirtine doesn't act on any sub unit related to T. ( So no possible impact)
- Retigabine acts on interspike interval, meaning less T. spikes and it can possibly repolarize the action potential for some people. But the sub unit range is too wide with numerous side effects. (so it can work to stabilize T. and decrease it to some extent, but is not specific enough to be viable.)
- AUT00063 acts directly on the repolarization and is much more precise, so it's a viable solution providing it works as expected
