Gaba

Introduction

Amino acids are the building molecules of proteins and have the most vital function in the human body. They also contribute to the synthesis of hormones and neurotransmitters.

 

Gamma-aminobutyric acid or GABA is the most potent inhibitory neurotransmitter in the central nervous system of mature individuals. It’s released from the spinal cord neurons, cerebellum, basal ganglia, and many cerebral cortex areas.

 

What Are the Functions of the GABA Inhibitory Neurotransmitter?

 

GABA’s natural function is to reduce the activity of the neuron cells to which it binds. When GABA attaches to a GABA receptor in the brain, it produces a calming effect.

 

This reduction of the neuronal excitability throughout the nervous system supports stress and fear regulation. Also, GABA is most commonly used for treating anxiety, high blood pressure, insomnia, fatigue, etc. It is also used for burning fat, stabilizing blood pressure, and relieving pain.

 

GABA receptor activity also participates in the prevention of seizures and has a significant role in behavior and learning.

 

GABA is also involved in the development of white matter neurons and the development of the oligodendrocytes.

What Is the Mechanism of Neurotransmission?

 

A multitude of complex chemical processes governs activity in the human brain. The neurotransmitters (ligands) continuously transmit an incalculable number of signals between the neurons received through a receptor – a protein of the membrane of neural cells to which a neurotransmitter, a drug, or a hormone can bind to and create a biochemical reaction in the brain.

What Are Agonists?

 

For the receptor to produce a biological response in the human brain, it needs to be activated by a chemical that binds to it, thus triggering its activation. An agonist, i.e., a drug that sets off the receptor’s natural response, is responsible for initiating this action.

What Are Antagonists?

 

However, a particular type of receptor-ligand, i.e., a chemical substance or drug that becomes a part of the biomolecule, blocking the bioreceptor’s logical response. These drugs are called antagonist drugs or blockers, because they inhibit, reduce, block, or reverse the neuron receptor’s action potential.

 

What Is Depolarization?

 

In depolarization, the neuronal cell’s negative internal charge temporarily becomes more positive (less negative). This change from a negative to a more positive membrane potential of the neuronal cell occurs during several complex chemical processes, including the action potential.

 

The neuron sends another electrical signal to change the electrical chargeback to a non-agitated state. Again, the entire process occurs when the cell allows specific ions to flow into and out of the neuronal cell. Thus, the positively charged potassium ions flow in the opposite direction, restoring the balance of the neuronal cell charge.

 

The GABA receptors are located in the postsynaptic membrane of the neuron cell. When two GABA molecules bind to its receptor, the receptor channel opens and makes way for the chloride ions to flow into the neuron.

 

GABA Receptors

 

GABA (GABAA and GABAB) receptors are located in the limbic system, a brain area dedicated to controlling and regulating personal feelings and storing emotional memories.

 

GABA receptors located on the nerve cells receive the chemical impulses that support the inhibition or reduction of the nerve impulses.

 

How Many GABA Receptors Are in the Brain?

 

There are two main types of GABA receptors – the ionotropic GABAA receptor (ligand-gated ion channels) and the metabotropic GABAB receptor (G protein-coupled receptors).

 

In the adult brain, the GABA receptor acts primarily through activation of the fast hyperpolarizing GABAA receptors. While the GABAA receptor reduces the neuronal excitability, the GABAB receptor leads to a decreased cyclic adenosine monophosphate (cAMP).

 

What Is the Role of GABA Receptor Agonist Drugs?

 

Many medications interact with GABA and GABA receptors in the brain, altering their function to achieve particular effects, typically relaxation, pain relief, stress and anxiety reduction, lower blood pressure, and improved sleep.

 

Barbiturates, anesthetics, benzodiazepines, antidepressants, and anti-seizure medications are some of the drugs that target GABA.

 

The GABA receptor agonist drugs produce the characteristic sedative, anxiolytic, anticonvulsant, and muscle relaxant effects.

 

The GABAA receptor list contains the following agonist drugs.

 

  • Abecarnil
  • Barbiturates
  • Bamaluzole
  • Fengabine
  • GABA
  • Gabamide
  • GABOB
  • Gaboxadol
  • Ibotenic acid
  • Isoguvacine
  • Isonipecotic acid
  • Muscimol
  • Pantherine
  • Phenibut
  • Picamilon
  • Progabide
  • Propofol
  • Quisqualamine
  • SL 75102
  • Thiomuscimol
  • Topiramate
  • Zolpidem
  • Eszopiclone

 

The GABAA receptor positive allosteric modulator list contains the following drugs.

 

  • Alcohols (e.g., ethanol, isopropanol)
  • Avermectins (e.g., ivermectin)
  • Barbiturates (e.g., phenobarbital)
  • Benzodiazepines (e.g., diazepam, alprazolam)
  • Bromides (e.g., potassium bromide)
  • Carbamates (e.g., meprobamate, carisoprodol)
  • Chloral hydrate, chloralose, petrichloral, and other 2,2,2-trichloroethane prodrugs
  • Chlormezanone
  • Clomethiazole
  • Etazepine
  • Etifoxine
  • 2-Substituted phenols (e.g., thymol, eugenol)
  • Imidazoles (e.g., etomidate)
  • Kavalactones (found in kava)
  • Loreclezole
  • Neuroactive steroids (e.g., allopregnanolone, ganaxolone)
  • Nonbenzodiazepines (e.g., zaleplon, zolpidem, zopiclone, eszopiclone)
  • Propofol
  • Piperidinediones (e.g., glutethimide, methyprylon)
  • Propanidid
  • Pyrazolopyridines (e.g., etazolate)
  • Quinazolinones (e.g., methaqualone)
  • Skullcap constituents
  • Stiripentol
  • Disulfonylalkanes (e.g., sulfonmethane, tetronal, trional)
  • Valerian constituents (e.g., valeric acid, valerenic acid)
  • Volatile organic compounds (e.g., chloroform, diethyl ether, sevoflurane)

 

The GABAB  receptor list contains the following agonist drugs.

 

  • 1,4-Butanediol
  • Baclofen
  • GABA
  • Gabamide
  • GABOB
  • gamma-Butyrolactone (GBL)
  • gamma-Hydroxybutyric acid (GHB)
  • gamma-Hydroxyvaleric acid (GHV)
  • gamma-Valerolactone (GVL)
  • Lesogaberan
  • Phenibut
  • Picamilon
  • Progabide
  • SL-75102
  • Tolgabide

What Are Benzodiazepines?

 

Benzodiazepines (sedatives) are psychoactive drugs that bind to the same receptors as GABA and mimic GABA’s natural calming effects. They increase the impact of the gamma-aminobutyric acid (GABA) at the GABAA receptor to decrease the excitability of neurons. Due to this, benzodiazepines are administered in the medical treatment for anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal, etc.

 

What Are the Types of Benzodiazepines?

 

There are 6 types of benzodiazepines:

 

  • 2-keto compounds: clorazepate, diazepam, flurazepam, halazepam, prazepam, and others
  • 3-hydroxy compounds: lorazepam, lormetazepam, oxazepam, temazepam
  • 7-nitro compounds: clonazepam, flunitrazepam, nimetazepam, nitrazepam
  • Triazolo compounds: adinazolam, alprazolam, estazolam, triazolam
  • Imidazo compounds: clonazolam, loprazolam, midazolam
  • 1,5-benzodiazepines: clobazam

 

What Are Benzodiazepines Used For??

 

Even though most benzodiazepines can be used interchangeably, some are most commonly used for particular medical conditions. The list of benzodiazepines contains the following drugs.

 

  • Diazepam (Valium) usually has an active effect within 30 to 60 minutes.
  • Oxazepam (Serax) has a slow start of effect, and lorazepam (Ativan), alprazolam (Xanax), and clonazepam (Klonopin) have intermediate start of effect
  • Clorazepate (Tranxene), midazolam (Versed), and triazolam (Halcion) are short-acting agents with a duration of action of 3 to 8 hours.
  • Alprazolam (Xanax), and temazepam (Restoril) are intermediate-acting agents with a duration of action of 11 to 20 hours.
  • Diazepam (Valium) and quazepam are long-acting agents that start acting in 1 to 3 days.
  • Alprazolam (Xanax), chlordiazepoxide (Librium), clorazepate (Tranxene), diazepam (Valium), lorazepam (Ativan), and midazolam are used for anxiety disorders.
  • Clonazepam (Klonopin), clorazepate (Tranxene), lorazepam (Ativan), clobazam (Onfi), and diazepam (Valium) are used for seizure disorders.
  • Estazolam (Prosom), flurazepam (Dalmane), quazepam (Doral), temazepam (Restoril), and triazolam (Halcion) are used for insomnia or trouble sleeping.
  • Lorazepam (Ativan) and diazepam (Valium) are used in anesthesia.
  • Diazepam (Valium) is also used for the relaxation of muscles.
  • Chlordiazepoxide (Librium) is used in cases of alcohol withdrawal.

 

What Happens if the GABA System in Our Brain Is Dysfunctional?

 

When we have a dysfunctional GABA system in our brains, the nerve cells fire more than they should, thus putting our brains in an excitatory state. The excess firing of the cells can lead to anxiety and feelings of panic, stress, restlessness, irritability; a decreased tolerance for pain; a fast heart rate; high blood pressure; insomnia, and occasional seizures.

 

What Are the Symptoms of Low GABA Activity in the Body?

 

Low GABA activity in the body can result in:

 

  • Anxiety;
  • Chronic stress;
  • Depression;
  • Difficulty concentrating and memory problems;
  • Muscle pain and headaches;
  • Insomnia and other sleep problems;
  • Agitation and different neuropsychiatric reactions (such as behavioral problems, hostility, hyperactivity, restlessness);
  • Dry mouth;
  • Fatigue;
  • Gastrointestinal upset (such as diarrhea or constipation, nausea, or vomiting);
  • A headache;
  • Nystagmus (repetitive, uncontrolled eye movements) and other eye disorders;
  • Pain (including back pain, chest pain, muscle and joint pain, and stomach pain);
  • Peripheral edema (swelling of the lower legs and feet);
  • Teeth grinding;
  • Tremor;
  • Weight gain.

What Are the Side Effects of GABA Supplements?

Some of the GABA supplements side effects include:

 

  • Upset stomach;
  • Headache;
  • Sleepiness;
  • Muscle weakness;
  • Gastric distress;
  • Nausea;
  • Lack of appetite;
  • Constipation;
  • Burning throat;
  • Drowsiness and fatigue;
  • Shortness of breath.

 

Fun Facts

Did you know?

 

  1. Fermented foods like kimchi, miso, and tempeh are examples of foods containing GABA.
  2. As a result of its properties, and the fact that it isn’t available from many food sources, GABA has found its place among the most popular supplements.
  3. GABA neurotransmitter is derived from glutamate – the most potent excitatory neurotransmitter of the central nervous system secreted by the neurons located in the central nervous system’s sensory pathways and the cerebral cortex.
  4. Sedatives are medications that slow down brain activity and calm the patient, ease agitation, and permit sleep. They are used to treat anxiety, tension, seizures, panic disorders, and sleep disorders.
  5. Anxiolytics are medications that inhibit anxiety. Hence, they are used for the treatment of various anxiety disorders, as well as related psychological and physical symptoms.
  6. Anticonvulsants (also: antiepileptic drugs or antiseizure drugs) are medications used to treat epileptic seizures. They prevent the spread of the seizure within the brain.
  7. The molecules that increase the GABAA receptor protein activity in the vertebrate central nervous system are called GABAA receptor positive allosteric modulator (PAM).
  8. A GABAergic drug is any chemical that modifies the effects of the GABA neurotransmitter in either the body or brain.
  9. The first benzodiazepine, chlordiazepoxide (Librium), was synthesized in 1955 by Leo Sternbach.
  10. Some of the strongest sedatives include Xanax (alprazolam), Valium (diazepam), Ativan (lorazepam), Librium (chlordiazepoxide), Halcion (triazolam), Serax (oxazepam), and Klonopin (clonazepam).