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Lamotrigine is an antiepileptic drug used to treat seizures. Off-label, it is used to treat a variety of neurological and psychiatric disorders. Judging from Google Scholar, lamotrigine continues to be the subject of active research: both on the neuroscience end to elucidate its mechanism of action, and on the clinical end to investigate its efficacy in treating disorders beyond its approved usage for seizures.

There are interesting statements in the literature regarding the neuroprotective effects of lamotrigine, for example:

... several studies have investigated LTG’s neuroprotective effects in models related to the toxic effects of glutamatergic agents. [1]

and

Like the other mood stabilizers lithium and valproate, LTG also has neuroprotective properties but its exact mechanisms remain poorly defined. [2]

There are additional, supporting studies cited within the previous two references. I believe this bibliography, though of course not exhaustive, is at least representative.

My question is this: What on earth is the relevance of these statements for real-life scenarios involving humans? Neurodegeneration is a relatively common occurrence in human populations, resulting from such diverse sources as toxins, physical injuries to the head, and aging. Based on what is known so far about the involved neurological mechanisms, could lamotrigine potentially protect against neurodegeneration in any of these cases?

One particular case that came to mind is neurodegeneration due to binge drinking. I have heard that neuronal cell loss in this case has been hypothesized to arise from glutamatergic mechanisms, which could be relevant for lamotrigine since lamotrigine is thought to suppress release of glutamate. On the other hand, this article calls into question the glutamatergic explanation for alcohol-induced brain damage:

... the mechanism [for binge-drinking induced brain damage] is not directly related to glutamate neurotoxicity. [3]

Another case that occurred to me is amnesic shellfish poisoning, an illness caused by the neurotoxin domoic acid, which has a strong affinity for glutamate receptors.

I'm not an expert in neuroscience and/or pharmacology, so I have limited ability to take 1) the theoretical understanding of lamotrigine's mechanism of action, and 2) the theoretical understanding of various neurodegenerative disorders; and make some hypothesis about a possible neuroprotective effect, if any.

Is it likely that lamotrigine could have neuroprotective effect against the two illnesses mentioned above? Or are there other examples?

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    $\begingroup$ I think this question has too many sub-questions packed in to it (SE prefers more focus). I would start with the original research describing a neuroprotective effect. "Neuroprotective" is not a specific term; there are lots of potential sources and mechanisms for brain damage, and it's unlikely that the same agent will be neuroprotective in all of them, just like seat belts might protect you in a car accident but not from a gunshot. I suspect they are specifically referring to neuroprotection during epileptic events given the context, though I did not actually read the papers you mention. $\endgroup$ – Bryan Krause Feb 5 '18 at 17:03
  • $\begingroup$ Right, I should have tried to narrow the question down more, or at least shortened the presentation. ~ Certainly it makes sense that lamotrigine should protect the brain during epileptic events -- after all, it is intended to prevent them in the first place. My question is whether this neuroprotective effect has implications for other scenarios of neurodegeneration. It may, however, be difficult to make the connection on a theoretical level since even the action of lamotrigine itself is poorly understood, and brain damage can stem from so many diverse sources, as you have explained. $\endgroup$ – CW_20161 Feb 10 '18 at 17:54

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