GABAB Receptors

GABAB receptors are metabotropic G-protein-coupled receptors (GPCRs) responsible for mediating the inhibitory effects of GABA, alongside ionotropic GABAA and GABAA receptors. They exist as heterodimers of GABAB1 and GABAB2 subunits, and are located on both pre- and post-synaptic membranes.

Products
Background
Literature (6)
Gene Data

Agonists

Cat. No. Product Name / Activity
0796 (R)-Baclofen
Selective GABAB agonist; active enantiomer of (RS)-Baclofen (Cat. No. 0417)
0417 (RS)-Baclofen
Selective GABAB agonist
0344 GABA
Endogenous agonist
3400 RuBi-GABA
Caged GABA; excitable at visible wavelengths
4709 RuBi GABA trimethylphosphine
Caged GABA; inhibits neural activity
0379 SKF 97541
Highly potent GABAB agonist; also GABAA-ρ antagonist

Antagonists

Cat. No. Product Name / Activity
1245 CGP 35348
Selective GABAB antagonist; brain penetrant
3219 CGP 36216 hydrochloride
GABAB antagonist; displays activity at presynaptic receptors
1247 CGP 46381
Selective GABAB antagonist; brain penetrant
1246 CGP 52432
Potent and selective GABAB antagonist
1088 CGP 54626 hydrochloride
Potent and selective GABAB antagonist
1248 CGP 55845 hydrochloride
Potent and selective GABAB antagonist
0245 2-Hydroxysaclofen
Selective GABAB antagonist; more potent than Saclofen (Cat. No. 0246)
0246 Saclofen
Selective GABAB antagonist
0984 SCH 50911
Selective and competitive GABAB antagonist; orally bioavailable

Modulators

Cat. No. Product Name / Activity
3313 rac BHFF
Potent and selective postitive allosteric modulator of GABAB receptors
1514 CGP 13501
Positive allosteric modulator of GABAB receptors
1513 CGP 7930
Positive allosteric modulator of GABAB receptors
2001 GS 39783
Positive allosteric modulator of GABAB receptors

Other

Cat. No. Product Name / Activity
1814 N-ArachidonylGABA
Inhibits pain in vivo
0538 trans-4-Hydroxycrotonic acid
GHB receptor ligand
0386 3-Methyl-GABA
Activator of GABA amino-transferase
1811 Modafinil
Psychostimulant
0780 NCS-382
Antagonist of γ-hydroxybutyric acid
4579 Pentobarbital sodium salt
Enhances GABAergic activity
2687 Pentylenetetrazole
CNS stimulant
5518 UMB 68
GHB receptor ligand
2815 Valproic acid, sodium salt
Increases GABA levels; anticonvulsant
2625 Zonisamide
Modulates GABA neurotransmission; anticonvulsant

GABAB receptors are GPCRs composed of seven transmembrane domains and a large extracellular N-terminal, and are responsible for mediating the inhibitory effects of GABA, alongside ionotropic GABAA and GABAA receptors. They are composed of 850 - 960 amino acids, and are most similar in structure to metabotropic glutamate receptors (mGluRs).

These receptors are heterodimers of GABAB1 and GABAB2 subunits. The GABAB1 subunit hosts the binding site for GABA and other ligands, while the GABAB2 subunit couples to Gi/o signaling proteins. The two subunits interact allosterically: GABAB1 increases coupling of GABAB2 to G proteins and GABAB2 increases agonist binding to GABAB1. Through their Gi/o coupling, GABAB receptors activate postsynaptic inward rectifier K+ channels (KIR channels; GIRK), decrease calcium conductance and inhibit adenylyl cyclase.

GABAB receptors are widely distributed within the central nervous system, and are found on pre- and post-synaptic membranes, but show low density. The highest concentrations are found in the cerebellum, frontal cortex and specific thalamic nuclei. They are also found on autonomic nerves in the periphery.

On the presynaptic membrane GABAB receptors inhibit neurotransmitter release, including acting as autoreceptors to regulate the release of GABA. When located on excitatory presynaptic terminals, they regulate glutamate release. These actions occur via the inhibition of Ca2+ channels, mediated by the G-protein β/γ subunits, and subsequent decrease in Ca2+ influx in response to an arriving action potential. Postsynaptic GABAB receptors mediate slow, inhibitory synaptic transmission, through the activation of KIR channels that mediate the late phase of the inhibitory postsynaptic potential.

Baclofen, a GABA derivative and GABAB agonist, is the only widely clinically available drug targeting the GABAB receptor. It was originally developed as a treatment of epilepsy, but showed disappointing results. It is now primarily used to treat spastic movement associated with multiple sclerosis and cerebral palsy. Baclofen has also been studied for the treatment of alcohol addiction. Similarly, activation of the GABAB receptor, with an agonist or a positive allosteric modulator, is thought to reduce the craving for addictive drugs, such as cocaine.

External sources of pharmacological information for GABAB Receptors :

Literature for GABAB Receptors

Tocris offers the following scientific literature for GABAB Receptors to showcase our products. We invite you to request* or download your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


GPCR

GPCR Product Listing

A collection of over 450 products for G protein-coupled receptors, the listing includes research tools for the study of:

  • Rhodopsin-like Receptors
  • Glutamate Receptors
  • Frizzled Receptors
  • GPCR Signaling
Pain

Pain Research Product Guide

A collection of over 280 products for pain research, the guide includes research tools for the study of:

  • Nociception
  • Ion Channels
  • G-Protein-Coupled Receptors
  • Intracellular Signaling
GABA Receptors

GABA Receptors Scientific Review

Written by Ian Martin, Norman Bowery and Susan Dunn, this review provides a history of the GABA receptor, as well as discussing the structure and function of the various subtypes and the clinical potential of receptor modulators; compounds available from Tocris are listed.

Addiction

Addiction Poster

The key feature of drug addiction is the inability to stop using a drug despite clear evidence of harm. This poster describes the brain circuits associated with addiction, and provides an overview of the main classes of addictive drugs and the neurotransmitter systems that they target.

Epilepsy

Epilepsy Poster

Epilepsy is a brain disease that affects 60 million people globally. More than 20 anti-seizure drugs are currently available, but these do not address the underlying causes of the condition. This poster summarizes current knowledge about the development of the condition and highlights some approaches that have disease-modifying effects in proof-of-concept studies.

Schizophrenia

Schizophrenia Poster

Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster describes the neurobiology of Schizophrenia, as well as highlighting the genetic and environmental factors that play a fundamental role in the etiology of the disease. The current and emerging drug targets are also discussed.

GABAB Receptor Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
GABAB1 Human GABBR1 NM_021905 Q9UBS5
Mouse Gabbr1 NM_019439 Q9WV18
Rat Gabbr1 NM_031028 Q9Z0U4
GABAB2 Human GABBR2 NM_005458 O75899
Mouse Gabbr2 NM_001081141 Q80T41
Rat Gabbr2 NM_031802 O88871