Lithium ions have known neuroprotective qualities. That would explain its therapeutic benefit in some mental disorders. It is also well known that lithium carbonate must be taken in toxic doses to get even small amounts into the brain. This makes lithium carbonate a very non-optimal medicine. On the other hand, lithium orotate promises to reach the brain much more efficiently and therefore require smaller doses. Unfortunately it contains orotic acid, which is a known carcinogen.

Magnesium L-threonate is a form of magnesium that easily penetrates the blood-brain barrier and therefore confers therapeutic effects on the brain. Is it then conceivable that lithium L-threonate is both safe and effective as a medicine for brain disorders?

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    $\begingroup$ Maybe yes? Perhaps the synthesis is easy, I believe that the metabolic route of l-threonate should be taken into account too. $\endgroup$ – Orr22 Dec 22 '15 at 13:14
  • $\begingroup$ Do you know why lithium ion has a good neuroprotective qualities? Is it because is small and has high redox potential? I never searched for this. $\endgroup$ – Orr22 Dec 22 '15 at 13:15
  • $\begingroup$ I’m pretty sure that elemental lithium is bad for the brain as it will immediately react with the water around to create $\ce{LiOH}$ which will cause even more damage … ;) $\endgroup$ – Jan Dec 23 '15 at 1:44
  • $\begingroup$ Jan, elemental lithium is good for the brain in trace amounts. Cities that have higher levels of lithium in the water supply have lower suicide rates, at least suggesting a potential connection. The fact that lithium carbonate is administered to mentally ill patients means it must have tonic effects on the brain. As stated in the original post, lithium carbonate is so inefficient at getting to the brain that toxic amounts must be used to get therapeutic results. $\endgroup$ – John Wilt Dec 23 '15 at 7:33
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    $\begingroup$ Consider also the fact that the positive charge is less polarizable on the small lithium compared to potassium. I am no pharmacologist but it may play a role for the permeation of the blood-brain barrier. $\endgroup$ – tschoppi Jan 23 '16 at 22:27

Lithium has a diagonal relathionship with magnesium, so in effect, it makes sense to compare it to magnesium compounds. It may also substitute for sodium ions in transporters. I doubt the counter ions is relevant, since most Li coumpounds are quantitatively dissociated. Stable concentrations of lithium are only achieved after several week of treatment. Lithium carbonate, citrate and sulfate are used to my knowledge. Plasma concentrations are monitored so as to avoid reaching toxic levels (more than 1 milli molar). Some physicians also test for the concentration inside red blood cells to get an idea of the concentration in the brain, but this has not been confirmed to be relevant. What is important is not the amount of it, but the clinical effect : is the patient responding to treatment ? does he/she support it ?

Lithium has not only neuroprotective effects, but also mood-stabilizing effects. It is mostly used in case of bipolar disorder (mood swings), but also as an antidepressant. The mechanism of action is still elusive. It may enhance serotonin pathway, and, by competing with magnesium ions, inhibit some magnesium-dependent enzymes (typically enzymes handling MgATP). One of these enzymes is called glycogen-synthase-kinase (GSK).

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