Gabapentin (Neurontin)

[BB23]

Did anyone realise this? It was my understanding it only worked on calcium channels.

Gabapentin Is a Potent Activator of KCNQ3 and KCNQ5 Potassium Channels

Quite frankly, Gabapentin was effective for me. I did feel a bit sedated and vague at 600mg/day. I woke up with blurred vision that settled after a couple of hours.

Aren't these the channels we are creaming over on XEN1101 and BHV-7000?

From the paper you posted:

Gabapentin efficacy was highest at −60 to −40 mV, leading to a −9 mV shift in the voltage dependence of KCNQ2/3 activation (1 µM gabapentin), but gabapentin also augmented currents at positive membrane potentials (Fig. 3, B and E). Dose-response studies showed that at −60 mV, gabapentin exhibited an EC50 value for KCNQ2/3 activation of 4.2 ± 0.13 nM (n = 5–7); at 10 nM, gabapentin increased KCNQ2/3 current 3.5-fold at −60 mV (Fig. 3F; Supplemental Fig. 1; Supplemental Table 1). The ability to activate KCNQ2/3 at subthreshold potentials enabled gabapentin to shift the membrane potential (EM) of KCNQ2/3-expressing oocytes by > −10 mV (EC50, 4.2 nM) (Fig. 3G). Parallel studies showed that pregabalin failed to activate KCNQ2/3 even at 1 µM, and began to inhibit KCNQ2/3 at 10 µM and above (Fig. 3, E and F; Supplemental Fig. 2; Supplemental Table 2). Pregabalin likewise failed to shift the oocyte EM (Fig. 3G). Compared with the established KCNQ2/3 opener and anticonvulsant retigabine, gabapentin acted as a potent partial agonist. Thus, retigabine (30 µM) shifted the voltage dependence of KCNQ2/3 activation by −30 mV (Fig. 3H) and increased current at −60 mV by 6-fold (Fig. 6I), however, the EC50 value for retigabine was in the micromolar (not nanomolar) range (Fig. 3J), which is ∼1000-fold less potent than gabapentin (see Supplemental Fig. 3; Supplemental Table 3). In comparison, we recently found that GABA, which also acts at KCNQ3-W265, activates KCNQ2/3 with an EC50 value of 0.85 µM at −60 mV, increasing the current by 4-fold (Manville et al., 2018). Thus, gabapentin and GABA exhibit similar efficacy but gabapentin is 200-fold more potent.

I think the highlighted parts in the excerpt gives us the reason why Gabapentin doesn't work as well as Retigabine, it just isn't as powerful as Retigabine at shifting voltages and increasing currents.

 

[momus]

This is so weird. I've been taking Gabapentin for about 6 or 7 years now as a sleep aid and for neuropathy in my hands. It also used to help w/ my tinnitus, but now I'm not too sure about that.

My tinnitus has been louder than normal lately, but I figured it might be due to seasonal allergies. After closely monitoring it, I think it could actually be due to the Gabapentin. Toward the end of the day, around my bedtime, my tinnitus has been pretty quiet, but tonight, it seemed to amp up not long after taking the Gabapentin. That's when I've noticed it being louder the past several weeks, too.

I found the usual web results of people using it FOR their tinnitus, and then stumbled onto an article where the patient stated it actually caused their tinnitus and mentioned that the PDR lists it as ototoxic. I haven't been able to find any reference to it being ototoxic using the online PDR though.

Has anyone else had issues w/ tinnitus and Gabapentin? I'm linking the article below where the patient says their doctor cited the Gabapentin as being responsible for their tinnitus. There are numerous articles where people say it helped theirs, so I didn't see any need to link those.

→ Veterans Benefits Network: Tinnitus After Taking Gabapentin?

 

[Nick47]

This is so weird. I've been taking Gabapentin for about 6 or 7 years now as a sleep aid and for neuropathy in my hands. It also used to help w/ my tinnitus, but now I'm not too sure about that.

My tinnitus has been louder than normal lately, but I figured it might be due to seasonal allergies. After closely monitoring it, I think it could actually be due to the Gabapentin. Toward the end of the day, around my bedtime, my tinnitus has been pretty quiet, but tonight, it seemed to amp up not long after taking the Gabapentin. That's when I've noticed it being louder the past several weeks, too.

Gabapentin certainly didn't cause your tinnitus, as you already had it. It does not cause inner ear damage, which only a few drugs are known to do. Your tinnitus likely just got worse over time, like many people's do.

 

[BB23]

Gabapentin certainly didn't cause your tinnitus, as you already had it. It does not cause inner ear damage, which only a few drugs are known to do. Your tinnitus likely just got worse over time, like many people's do.

Don't speak in absolutes when it comes to drugs. Only clueless doctors do that.

They can cause adverse and paradoxical reactions, no matter the drug. They could cause the problems they were originally designed to fix.

It all depends on your individual CNS and its current status, your past drug history, or whether your CNS was sensitized or not by the drugs you took in the past, etc...

 

[grate_biff]

They can cause adverse and paradoxical reactions

I would have put my money on tolerance!

 

[RunningMan]

This is so weird. I've been taking Gabapentin for about 6 or 7 years now as a sleep aid and for neuropathy in my hands. It also used to help w/ my tinnitus, but now I'm not too sure about that.

What is your daily dosage? Have you increased it? Does it still work as well as a sleep aid after all those years?

It seems reports I always read say it either helps or doesn't affect tinnitus.

 

[StoneInFocus]

Has Gabapentin ever helped anyone with stabbing hyperacusis pain?

 

[linearb]

Has Gabapentin ever helped anyone with stabbing hyperacusis pain?

I was having some of this post-COVID-19 after my ears got super fed by it, and after finding a couple of papers, I jumped up to 600 mg/day for a couple of weeks. This coincided with a reduction in symptoms, but that could be a coincidence.

I've since stopped taking Gabapentin, mostly because I managed to forget to take it for about six days in a row, and when I realized that had happened and also I didn't feel much different, I thought, "Cool, there's one less drug I am using."

I think COVID-19 has some specific audio risks associated with it, and what happens post-COVID-19 may or may not have much to do with other kinds of tinnitus. COVID-19 appears to be able to directly infect cells in the inner ear in a way that other common respiratory viruses do not.

 

[ellees]

I'm thinking about Gabapentin

Did you ever try Gabapentin? Did it worsen or improve your tinnitus?

Did any of you experience tinnitus caused by benzodiazepines or antidepressants, and if so, did Neurontin help?

Is this question reflective of your experience? Do you have antidepressant-related tinnitus? Have you tried gabapentin, and if so, has it affected your tinnitus in any way?