GABA Reuptake Inhibitors (GRIs) function by inhibiting the reuptake of the neurotransmitter GABA (gamma-aminobutyric acid). The inhibition of GABA reuptake inevitably leads to more gamma-aminobutyric acid between synapses. The effects of GRI medications typically involve decreasing arousal in the central nervous system, leading to anxiolytic effects, sedation, and altered states of consciousness.
These medications are known to impair concentration, relax muscles, and are prescribed for a variety of conditions. These medications are often used to treat epileptic seizures and convulsions. In other cases they are prescribed for the management of anxiety disorders, insomnia, muscle relaxants, and to ease chronic pain.
GABA Reuptake Inhibitors List
Below is a list of documented GABA reuptake inhibitors. Keep in mind that some of these substances are merely drugs that are used for scientific research and have not been approved for human usage.
- Adhyperforin: This is a plant-based chemical that is derived from the Hypericum family of plants, most notably St. John’s Wort. It is considered to function similar to that of hyperforin and inhibits the reuptake of GABA as well as a variety of other neurotransmitters such as: serotonin, norepinephrine, dopamine, and glutamate.
- CI-966: This is an anticonvulsant drug that was initially studied in animal research. It was found to elicit GABA reuptake inhibition properties, but was not considered safe for usage in humans. In a study involving gerbils that had suffered ischemic strokes, it was found to make symptoms worse. Preliminary evidence suggested that this drug would end up being more harmful than beneficial.
- Deramciclane (EGIS-3886): This is a drug that has GABA reuptake inhibition properties in addition to functioning primarily as a 5-HT2A receptor antagonist and 5-HT2C receptor agonist. It was co-developed by the pharmaceutical companies Orion Pharma and Pharmacia (based in Finland) and was inevitably discontinued due to poor efficacy. It was initially developed for the treatment of generalized anxiety disorder and was hypothesized to work by increasing both serotonin and GABA.
- Guvacine: This is an alkaloid that is derived from the Areca nuts also sometimes referred to as “Betel” nuts. It is widely considered an experimental substance that currently has no medically accepted use. Its full mechanism of action is somewhat unclear, although it has been documented as a specific GABA reuptake inhibitor. Further research is underway to determine whether this drug may provide medical benefit.
- Hyperforin: This is a plant-based chemical that is derived from the Hypericum species, most commonly Hypericum perforatum (St. John’s Wort). This particular substance functions similar to adhyperforin in that it acts as a reuptake inhibitor of GABA. It has a stronger affinity for norepinephrine and dopamine, but affects serotonin to a lesser extent than GABA. It elicits its GABAergic effect primarily via activation of the TRPC6 ion channel, which allows both calcium and sodium to enter to enter the cell – leading to the reuptake inhibition.
- Nipecotic acid: This is a compound that is often used to inhibit the reuptake of GABA. It isn’t used for any medical purposes, but is often used for research purposes. It is created by chemical companies and can be purchased specifically for scientific studies.
- NNC-711: This drug is considered a very potent GABA retupake inhibitor and carries selective properties. It hasn’t been tested in humans, but is sometimes used in scientific research such as in mice. It is capable of reducing seizures and has significant anticonvulsant properties in the rodent population. Like other GABAergic medications, it is known to impair motor skills.
- SKF-89976A: This is yet another selective GABA reuptake inhibitor particularly as a GAT-1 blocker. It is thought to elicit slight anticonvulsant effects among rodents. This substance is not used in humans and is typically only used for select scientific research.
- Tiagabine (Gabitril): This is an anticonvulsant drug that was initially created in the late 1980s by a team of Dutch scientists and is approved by the FDA to treat partial seizures. It functions primarily by inhibiting the reuptake of GABA, thus increasing the amount of this neurotransmitter in the brain. It is currently manufactured by Cephalon Inc. and is sometimes prescribed as an off-label treatment for panic disorder and neuropathic pain management.
Conditions treated with GABA Reuptake Inhibitors
The GABA reuptake inhibitor class of drugs is generally prescribed for the treatment of seizures. Therefore an individual who has had convulsions, partial seizures, and/or is diagnosed with epilepsy may be taking a GRI medication.
- Partial Seizures
In other cases, the GABA reuptake inhibitors are prescribed as a second or third line treatment option for other conditions like anxiety, insomnia, neuropathic pain, and panic disorder. Depending on the individual, GRI medications may be used as an adjunct treatment with first-line treatments.
- Muscle relaxation
- Neuropathic pain
- Panic disorder