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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. [1]
Tolerance to gabapentinoids is reported to develop very rapidly with repeated use, although to also dissipate quickly upon discontinuation, and withdrawal symptoms such as insomnia, nausea, headache, and diarrhea have been reported. [58] [21] More severe withdrawal symptoms, such as severe rebound anxiety, have been reported with phenibut. [30]
Withdrawal symptoms occur during dose reduction and may include insomnia, anxiety, distress, weight loss, dizziness, night sweats, shaking, muscle twitches, aphasia, panic attacks, depression, dissociation, paranoia, indigestion, diarrhea, and photophobia. As withdrawal progresses, patients often find their physical and mental health improves ...
Gabapentin is recommended as a first-line treatment for chronic neuropathic pain by various medical authorities. [10] [11] [31] [32] This is a general recommendation applicable to all neuropathic pain syndromes except for trigeminal neuralgia, where it may be used as a second- or third-line agent. [11] [32]
The GABA A receptor is a protein complex located in the synapses between neurons. All GABA A receptors contain an ion channel that conducts chloride ions across neuronal cell membranes and two binding sites for the neurotransmitter gamma-aminobutyric acid (GABA), while a subset of GABA A receptor complexes also contain a single binding site for ...
Although anxiety can temporarily increase as a withdrawal symptom, there is evidence that a reduction or withdrawal from benzodiazepines can lead to a reduction of anxiety symptoms in the long run. [4] [5] Due to these increasing physical and mental symptoms from long-term use of benzodiazepines, slow withdrawal is recommended for long-term users.
Individuals who have had more withdrawal episodes are at an increased risk of very severe withdrawal symptoms, up to and including seizures and death. Long-term activation of the GABA receptor by sedative–hypnotic drugs causes chronic GABA receptor downregulation as well as glutamate overactivity, which can lead to drug and neurotransmitter ...
Rebound anxiety, more severe than baseline anxiety, is also a common withdrawal symptom when discontinuing diazepam or other benzodiazepines. [80] Diazepam is therefore only recommended for short-term therapy at the lowest possible dose owing to risks of severe withdrawal problems from low doses even after gradual reduction. [81]
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