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.
Indications
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.
Effects
GRIs can induce a wide range of psychological and physiological effects, including:
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 dyspnea or shortness of breath
Many of these properties are dependent on whether the GRI in question is capable of crossing the blood-brain-barrier (BBB). Those that do not will only produce peripheral effects.
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.
Overdose
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 brain damage death
List of GRIs
CI-966
Deramciclane (EGIS-3886) Gabaculine Guvacine (C10149) Nipecotic acid NNC 05-2090 NNC-711 SKF-89976A SNAP-5114 Tiagabine (Gabitril) Hyperforin