Lyrica -- glutamate -- Gabapentin

[wantok]

I was given Gabapentin more than one time and kept increasing the dose to a point where I got depresssed before it was stopping my leg movements (PLMs). I was told by Dr. B that I would get depressed on Lyrica so he recommended not to bother trying it. I tried it and at the lowest dose, from the first night, my legs stopped. In trying to figure out why I had such a different response to drugs that are considered to be practically identical I discovered that Gabapentin does not reduce glutamate but Lyrica does.

Years ago I discovered some of the epilepsy community trying glutamate-free diets with success. I tried but it is a very difficult diet (there is glutamate in practically everything) and I gave up after a while.

Why would the experts in the field (Dr. B obviously) represent these drugs as basically the same? I am assuming Lyrica's reduction of glutamate is the answer to my query regarding what the difference was in the success with one and not the other. Of course this could be by something else but it seem so significant to me that Lyrica reduces glutamate.

Comments anyone?

[QyX]

I did some quick google research and I honestly would be surprised, if Gabapentin doesn't have similar effects on the glutamate system than Lyrica.

Orally administered gabapentin (GBP), a GABA analog and anticonvulsant that is easily absorbed and crosses the blood–brain barrier, has shown promise in treating seizures and neuropathic pain. It is currently approved to treat seizure disorders by decreasing seizure activity presumably via increasing GABAergic tone and counter-balancing glutamatergic excitability.

Mechanistically, Gabapentin is thought to normalize GABAergic tone via stimulating GABA synthesis and to affect glutamate (Glu) production in both neurons and glia thereby affecting the excitability of postsynaptic membranes.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862797/

There is more that can be found but this was the first source I found. Also Pregabalin (Lyrica) and Gabapentin are indeed very similar. Pregabalin is basically a more potent version of Gabapentin. They are chemically closely related and are in the same class of drugs called Gabapentinoids.

More here: https://en.wikipedia.org/wiki/Gabapentinoid

I never tolerated Lyrica (Pregabalin) and Gabapentin wasn't much better. It is kind of reasonable to assume that when you have a bad reaction to one drug from a certain group that you most likely will have a bad reaction if you take another drug from the same class. It was probably his clinical experience that made him say that.

Additionally, I think it is an oversimplification when we think about in simple terms like increasing and decreasing dopamine / glutamate / serotonin or whatever because no matter what you do. Aspects like receptor sensitivity and receptor density are just as relevant as the concentration of certain neurotransmitters in the synaptic cleft and neuron itself. And even in the neuron itself the neurotransmitter are not all just in one location.

Maybe a better way to describe the effects of certain drugs is to look what the net results are. For example: are you stimulating or are you inhibiting glutamate neurotransmission?

Does this make sense?

[wantok]

Thanks for looking into this. From how I read the first quote, does it assume or imply that Gabapentin "decreases" glutamate? It doesn't sound very declarative; more like it "should be expected to."

It certainly is possible I am not understanding what I am reading.

"Mean glutamate concentrations did not change significantly with or without drug administration (of Gabapentin)." from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499716/ "The Impact of Gabapentin on GABA and glutamate" (more or less the title). The other studies I looked at were admittedly in rats but did show no decrease of glutamate with Gabapentin administration.

I am not sure how your last question modifies what I am saying?

Thanks again.

[QyX]

I just wanted to add some context. In my opinion you can't ask the question if Gabapentin increases / decreases glutamate for the reasons I outlined in my posts above.

Or if I maybe try to frame it in a different way.

You write:

Of course this could be by something else but it seem so significant to me that Lyrica reduces glutamate.

Okay, so where would Lyrica reduce glutamate? What do you even mean by that? The total amount of glutamate in the body? The amount of glutamate in the blood or in the central nervous system? When we talk about the central nervous system, do we talk about intracellular or extracellular concentrations?

When you say Lyrica reduces glutamate, it really doesn't mean anything without additional context.