GABA reuptake inhibitor
A GABA reuptake inhibitor (GRI) is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid (GABA) by blocking the action of the gamma-Aminobutyric acid transporters (GATs). This in turn leads to increased extracellular concentrations of GABA and therefore an increase in GABAergic neurotransmission.
GRIs may be used in the clinical treatment of seizures, convulsions, or epilepsy as anticonvulsants/antiepileptics, anxiety disorders such as generalized anxiety disorder (GAD), social phobia (SP) also known as social anxiety disorder (SAD), and panic disorder (PD) as anxiolytics, insomnia as hypnotics, muscle tremors or spasms as muscle relaxants, and chronic pain as analgesics. They may also potentially be used as anesthetics in surgery.
GRIs can induce a wide range of psychological and physiological effects, including a general and subjective alteration in consciousness, dizziness, blurry vision, diplopia or double vision, nystagmus or involuntary eye movements, amblyopia or “lazy eye”, tinnitus or “ear ringing“, sedation, drowsiness or somnolence, narcolepsy, tiredness or weakness, fatigue or lethargy, aches and pains, headache, nausea and vomiting, gastrointestinal disturbances, shakiness, disorientation, diminished awareness, impaired attention, focus, and concentration, decreased drive and motivation, stuttering and slurring of speech, confusion, cognitive and memory impairment, mood lift or drop, depression, anxiolysis, disinhibition, stress reduction, euphoria or dysphoria, irritability, aggression, anger or rage, increased appetite and subsequent weight gain, ataxia or impaired coordination and balance, muscle relaxation, trembling or muscle tremors and spasms, paresthesia or “pins and needles”, analgesia, respiratory depression, and dyspnea or shortness of breath, among others.
GRIs such as CI-966 have been characterized as hallucinogens with effects analogous to those of the GABAA receptor agonist muscimol (a constituent of Amanita muscaria (fly agaric) mushrooms) when administered at sufficient doses.
At very high doses characterized by overdose, a number of symptoms may come to prominence, including severe cognitive deficit to the point of acute retardation, anterograde or retrograde amnesia, drooling, piloerection or “goose bumps”, agitation or restlessness, flailing, thrashing, and screaming, unintentional or accidental injury, delirium, hallucinations, myoclonus, dystonia, paralysis, stupor, faintness or loss of consciousness, seizures or convulsions, status epilepticus, coma, and respiratory arrest or cessation of breathing, potentially resulting in hospitalization, brain damage, and/or death.
List of GRIs
- Hollister, Leo E. (1990). “New class of hallucinogens: GABA-enhancing agents”. Drug Development Research. 21 (3): 253–256. doi:10.1002/ddr.430210311. ISSN 0272-4391.
- Borden LA, Murali Dhar TG, Smith KE, Weinshank RL, Branchek TA, Gluchowski C (1994). “Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1”. Eur J Pharmacol. 269 (2): 219–224. doi:10.1016/0922-4106(94)90089-2. PMID 7851497.
- Wonnemann, M; Singer, A; Müller, WE (August 2000). “Inhibition of Synaptosomal Uptake of 3H-L-glutamate and 3H-GABA by Hyperforin, a Major Constituent of St. John’s Wort The Role of Amiloride Sensitive Sodium Conductive Pathways”. Neuropsychopharmacology. 23 (2): 188–197. doi:10.1016/S0893-133X(00)00102-0. PMID 10882845.
- Carlson, Neil R.; Birkett, Melissa (2017). Physiology of Behavior (12 ed.). Pearson. p. 103. ISBN 9780134320823.