Glutamate Transporter Boosting Medications
Propentofylline increases the expression of both the GLT-1 and GLAST glutamate transporters expression in vitro, and significantly enhanced glutamate uptake in astrocytes.
1 2 Propentofylline oral bioavailability is only 4%. Propentofylline half life of 15 – 45 minutes.
Note that the study used high concentrations of propentofylline (100 microM), which would equate to very high human oral dosages of 30 grams of propentofylline (taking into account the low 4% bioavailability). Transdermal application of propentofylline would be the best idea, as this avoids the first-pass metabolism, but the very high dosage of 30 grams probably makes propentofylline unusable for practical purposes for enhancing glutamate uptake.
Riluzole (a drug for ALS) at a dose of 160 mg elevates GLT-1 glutamate transporter expression and activity.
1 2 Riluzole bioavailability is 60%. Riluzole half-life is 12 hours. Riluzole costs around $1.50 for a 50 mg tablet.
Ceftriaxone (Rocephin) an injectable beta-lactam antibiotic that increases GLT-1 glutamate transporter expression and activity by
a factor of 3, which is a huge increase.
1 2 3 4 5 6 Ceftriaxone half life is around 7 hours. A single 500 mg ceftriaxone injection costs around $14.
Amoxicillin is a beta-lactam antibiotic that increases GLT-1 glutamate transporter expression by 500%.
1 Amoxicillin is quite cheap: you can get 500 x 500 mg capsules for around $60.
Citicoline (a cognitive enhancing supplement) at a dose of 2000 mg per kg in rats increases glutamate uptake and increases the expression of the GLT-1 glutamate transporter in cultured rat astrocytes. The equivalent human dose would be 323 mg per kg, which would work out to a 26 gram oral dose for an 80 kg human (which is far too high to make it viable).
1 Citicoline bioavailability is virtually 100%. Citicoline half life is 3.5 hours.
Valproic acid at a dose of 100 mg per kg in rats increased the expression of glutamate transporter GLT-1 after stroke.
1 The equivalent human dose would be 16 mg per kg.
Alpha lipoic acid at dose of around 270 mg to 1370 mg increases glutamate uptake by 20%.
1 Alpha lipoic acid bioavailability is around 30%. Half life is around 30 minutes.
Pyroglutamate stimulates glutamate transporter activity.
1 2 Pyroglutamic acid is available as a supplement. Arginine pyroglutamate is also available as a supplement.
Morphine withdrawal increases glutamate uptake, and increases the expression of the glutamate transporter GLT-1 in the hippocampus.
1 (This might potentially explain why some ME/CFS patients experience major improvements in their symptoms the in the days
after taking opioid pain killers, but not during the opioid treatment. See
this thread for more info of this interesting opioid effect).
Low-dose naltrexone may increase astrocyte glutamate transport.
1
Reactive oxygen species hydrogen peroxide and peroxynitrite impair glutamate transport into astrocytes.
1
Intranasal insulin? Insulin increases the expression of the GLT1 glutamate transporter in cultured astrocytes.
1
Factors that Reduce Glutamate Transport and Clearance
Low oxygen, due to inadequate blood supply (ischemia), raises glutamate levels.
TNF-α, IL-1β and IL-6 reduce clearance of glutamate.
4-hydroxynonenal significantly impair glutamate uptake.
1 4-Hydroxynonenal is generated in the oxidation of lipids containing polyunsaturated omega-6 acyl groups, such as arachidonic or linoleic groups.
Glutamate Transporter Nomenclature
Glutamate transporter (GLT-1) is also called the excitatory amino acid transporter 2 (EAAT2). Glutamate aspartate transporter (GLAST) is also called the excitatory amino acid transporter 1 (EAAT1). GLT-1 plays the predominant role in regulating extracellular glutamate; it is responsible for clearing 90% of the glutamate from the brain.
