Five amino acids are dispensable in humans, meaning they can be synthesized in sufficient quantities in the body. These five are alanine, aspartic acid, asparagine, glutamic acid and serine (i.e., A D N E S).
The glutamate neurotransmitter plays the principal role in neural activation. This anion is also responsible for the savory flavor (umami) of certain foods, and used in glutamate flavorings such as MSG.
Glutamic acid is used by almost all living beings in the biosynthesis of proteins, being specified in DNA by the codons GAA or GAG. It is non-essential in humans, meaning the body can synthesize it.
Since glutamates are important neurotransmitters in the human brain, playing a key role in learning and memory, ongoing neurological studies indicate a need for further research.
27. Nicholas J. Maragakis, MD; Jeffrey D. Rothstein, MD (March 2001). "Glutamate Transporters in Neurologic Disease". 58 (3). pp. 365–370. Retrieved 2015-01-17.
Punjab Food Authority banned MSG from being used in food products in January 2018 on it being detrimental to general, and particularly cardiovascular, health.
Exogenous GABA does not penetrate the blood–brain barrier; it is synthesized in the brain. It is synthesized from glutamate using the enzyme glutamate decarboxylase (GAD) and pyridoxal phosphate (which is the active form of vitamin B6) as a cofactor. This process converts glutamate, the principal excitatory neurotransmitter, into the principal inhibitory neurotransmitter (GABA).
GABA is converted back to glutamate by a metabolic pathway called the GABA shunt.
Tiagabine, a drug used as an anticonvulsant, acts by inhibiting the GABA transporter 1.
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.
However, 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.
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.