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.

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 GABA_A receptor agonist muscimol (a constituent of Amanita muscaria (fly agaric) mushrooms) when administered at sufficient doses.^[1]

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

^{[citation needed]}

List of GRIs[]

References[]

^ 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.
^ Jump up to: ^a ^b ^c ^d 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.

[Hollister1990-1] 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.

[pmid7851497-2] Jump up to: ^a ^b ^c ^d 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.

[pmid10882845-3] 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.

[1]

[2]

[3]