Baclofen (original) (raw)

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Description

A medication used to relieve severe muscle spasms caused by certain conditions in the brain and spinal cord.

Description

A medication used to relieve severe muscle spasms caused by certain conditions in the brain and spinal cord.

DrugBank ID

DB00181

Type

Small Molecule

US Approved

YES

Other Approved

YES

Therapeutic Categories

• gamma-Aminobutyric Acid-ergic Agonist

Mechanism of Action

• Gamma-aminobutyric acid type B receptor subunit 2
  Agonist

Summary

Baclofen is a GABA-ergic agonist used to manage severe spasticity of cerebral or spinal origin in adult and pediatric patients.

Brand Names

Fleqsuvy, Gablofen, Kemstro, Lioresal, Lyvispah, Ozobax

Generic Name

Baclofen

DrugBank Accession Number

DB00181

Background

Baclofen is a gamma-aminobutyric acid (GABA) agonist used as a skeletal muscle relaxant. Although originally designed in 1962 to treat epilepsy, baclofen was not effective in treating this condition but instead was shown to reduce spasticity in selected patients.8 Baclofen was reintroduced in 1971 as a treatment for spasticity and was later approved by the FDA in 1977.6,8 Baclofen is used to manage severe muscle spasms of cerebral or spinal cord origins, including multiple sclerosis and traumatic brain injury.11

Baclofen was investigated for use in alcohol dependence and withdrawal; however, evidence is limited and there is inconsistent evidence to suggest its clinical efficacy in managing alcohol dependence or withdrawal symptoms.1,2,8

Type

Small Molecule

Groups

Approved

Structure

Weight

Average: 213.661
Monoisotopic: 213.05565634

Chemical Formula

C10H12ClNO2

Synonyms

• (+-)-Baclofen
• 4-Amino-3-(4-chlorophenyl)butyric acid
• Baclofen
• Baclofène
• Baclofeno
• Baclofenum
• beta-(4-Chlorophenyl)gaba
• beta-(Aminomethyl)-4-chlorobenzenepropanoic acid
• beta-(Aminomethyl)-p-chlorohydrocinnamic acid
• beta-(p-Chlorophenyl)-gamma-aminobutyric acid
• DL-4-Amino-3-p-chlorophenylbutanoic acid
• DL-Baclofen
• gamma-Amino-beta-(p-chlorophenyl)butyric acid

Indication

Oral baclofen is indicated for the treatment of spasticity resulting from multiple sclerosis and is particularly useful for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. It may also be used to treat patients with spinal cord injuries and other spinal cord diseases. Baclofen should not be used to treat skeletal muscle spasms resulting from rheumatic disorders.12

Intrathecal baclofen is also indicated for the management of severe spasticity of the cerebral or spinal original in patients 4 years of age and older. It is reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable central nervous system side effects at effective doses. For use in spasticity due to traumatic brain injury, baclofen should be considered after at least one year of injury.11

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Associated Conditions

Contraindications & Blackbox Warnings

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Pharmacodynamics

Baclofen is an antispasmodic agent that induces muscle relaxation. It reduces the release of excitatory neurotransmitters in the pre-synaptic neurons and stimulates inhibitory neuronal signals in the post-synaptic neurons.6 Oral formulations of baclofen are the most commonly used form of the drug. In one cross-section study, intrathecal baclofen was more effective than oral baclofen in relieving spasticity directly at the level of the spinal cord.8 Baclofen has CNS depression properties and can cause sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression.13 Baclofen also mediates some antinociceptive effects and stimulates gastric acid secretion.15

Baclofen exhibits anti-inflammatory and neuroprotective activities: it inhibits the release of pro-inflammatory cytokines from microglia and astrocytes, and decreases oxidative stress in rats.5

Mechanism of action

The exact mechanism of action of baclofen is unclear. Baclofen is an agonist at the beta subunit of gamma-aminobutyric acid (GABA) receptors expressed on pre- and post-synaptic neurons.3 Upon binding to GABAB receptors, baclofen causes an influx of potassium into the neuron, leading to hyperpolarization of the neuronal membrane and decreased calcium influx at presynaptic nerve terminals. This results in a decreased rate of action potential threshold being reached by presynaptic neurons and reduced action potential of postsynaptic motor neurons that innervate the muscle spindles. Baclofen thereby inhibits the transmission of both mono- and polysynaptic reflexes at the spinal cord, relaxing spasticity.8 Baclofen may act on some voltage-gated calcium channels; however, the clinical significance of this is unclear.6

Absorption

Baclofen has an oral bioavailability of 70% to 85%. Following oral administration, it is rapidly absorbed through the gastrointestinal tract with peak plasma concentrations being reached two to three hours after ingestion.6 Peak effect is observed about four hours after intrathecal administration.8 The absorption is dose-dependent and increases with higher doses.6 There is intersubject variation in absorption.13

Administration of oral baclofen suspension with a high-fat meal resulted in 9% decrease in AUC and 33% decrease in Cmax compared to the fasted state.13

Volume of distribution

The volume of distribution of baclofen is 0.7 L/kg.15 As baclofen is mainly water-soluble, it does not readily cross the blood-brain barrier.7 Drug concentrations of baclofen in the cerebrospinal fluid are approximately 8.5 times lower than in the plasma.15

Protein binding

The protein binding is approximately 30%.15

Metabolism

Approximately 15% of the oral dose is metabolized in the liver, mainly by deamination.8 Deamination yields the main metabolite, β-(p-chlorophenyl)-4-hydroxybutyric acid, which is pharmacologically inactive.15

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Route of elimination

About 70-80% of baclofen is eliminated in an unchanged form by renal excretion 6,8 within 72 hours of administration. About 5% of the dose is excreted via the kidneys as metabolites.15 There is intersubject variation in elimination.13

Half-life

The half-life is 2-6 hours after oral administration and 1-5 hours following intrathecal administration.8 The apparent elimination half-life of baclofen oral suspension or granules is about 5.6 hours.13

Clearance

The systemic clearance (CL/F) was 180 mL/min and the renal clearance was 103 mL/min following oral administration.10

Adverse Effects

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Toxicity

The oral LD50 in rats is 145 mg/kg.14

Baclofen withdrawal symptoms typically occur within hours to days following interruption of either oral or intrathecal drug formulations.8 Abrupt discontinuation of baclofen is not advised.11 Clinical manifestations of baclofen overdose may include altered mental status, somnolence, seizure, hypothermia, respiratory depression, and coma. Overdose from baclofen oral tablets resulted in vomiting, lightheadedness, drowsiness, muscular hypotonia, accommodation disorders, coma, respiratory depression, and seizures.6,13 Most overdose symptoms are neurological but uncommon cardiovascular effects such as hypertension, bradycardia, and tachycardia may be observed.9 In case of overdose, symptomatic treatment and gastric decontamination should be initiated. When the patient is alert, gastric emptying should be performed by inducing emesis and then performing lavage while maintaining an adequate airway and respiration. Emesis should not be induced in unconscious patients.6,13

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Food Interactions

• Avoid alcohol.
• Take with food. Take with food or milk to reduce gastric irritation.

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Product Ingredients

Product Images

International/Other Brands

Baclon (Uniao Quimica (Brazil)) / Lioresal Intrathecal (Novartis Pharmaceuticals) / Nu-Baclofen (Nu-Pharm)

Brand Name Prescription Products

Generic Prescription Products

Unapproved/Other Products

ATC Codes

M03BX01 — Baclofen

• M03BX — Other centrally acting agents
• M03B — MUSCLE RELAXANTS, CENTRALLY ACTING AGENTS
• M03 — MUSCLE RELAXANTS
• M — MUSCULO-SKELETAL SYSTEM

Drug Categories

• Agents Causing Muscle Toxicity
• Amino Acids
• Amino Acids, Peptides, and Proteins
• Aminobutyrates
• Butyrates
• Central Nervous System Agents
• Central Nervous System Depressants
• Drugs that are Mainly Renally Excreted
• GABA Agents
• GABA Agonists
• GABA-B Receptor Agonists
• Gaba-derivative Skeletal Muscle Relaxants
• gamma-Aminobutyric Acid-ergic Agonist
• Muscle Relaxants
• Muscle Relaxants, Centrally Acting Agents
• Muscle Relaxants, Peripherally Acting Agents
• Musculo-Skeletal System
• Neurotransmitter Agents

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Gamma amino acids and derivatives

Alternative Parents

Phenylpropanoic acids / Chlorobenzenes / Aralkylamines / Amino fatty acids / Aryl chlorides / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organochlorides / Organic oxides / Monoalkylamines / Hydrocarbon derivatives / Carbonyl compounds show 4 more

Substituents

3-phenylpropanoic-acid / Amine / Amino acid / Amino fatty acid / Aralkylamine / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Benzenoid / Carbonyl group / Carboxylic acid / Chlorobenzene / Fatty acyl / Gamma amino acid or derivatives / Halobenzene / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organochloride / Organohalogen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Primary aliphatic amine / Primary amine show 18 more

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

monocarboxylic acid, primary amino compound, monochlorobenzenes, gamma-amino acid (CHEBI:2972)

Affected organisms

• Humans and other mammals

UNII

H789N3FKE8

CAS number

1134-47-0

InChI Key

KPYSYYIEGFHWSV-UHFFFAOYSA-N

InChI

InChI=1S/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14)

IUPAC Name

4-amino-3-(4-chlorophenyl)butanoic acid

SMILES

NCC(CC(O)=O)C1=CC=C(Cl)C=C1

Synthesis Reference

US5843765

General References

1. Brennan JL, Leung JG, Gagliardi JP, Rivelli SK, Muzyk AJ: Clinical effectiveness of baclofen for the treatment of alcohol dependence: a review. Clin Pharmacol. 2013 Jul 3;5:99-107. doi: 10.2147/CPAA.S32434. Print 2013. [Article]
2. Liu J, Wang LN: Baclofen for alcohol withdrawal. Cochrane Database Syst Rev. 2017 Aug 20;8:CD008502. doi: 10.1002/14651858.CD008502.pub5. [Article]
3. Chen K, Li HZ, Ye N, Zhang J, Wang JJ: Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro. Brain Res Bull. 2005 Oct 30;67(4):310-8. doi: 10.1016/j.brainresbull.2005.07.004. [Article]
4. Fu Z, Yang H, Xiao Y, Zhao G, Huang H: The gamma-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens. Behav Brain Funct. 2012 Jul 10;8:20. doi: 10.1186/1744-9081-8-20. [Article]
5. de Beaurepaire R: A Review of the Potential Mechanisms of Action of Baclofen in Alcohol Use Disorder. Front Psychiatry. 2018 Oct 17;9:506. doi: 10.3389/fpsyt.2018.00506. eCollection 2018. [Article]
6. Ghanavatian S, Derian A: Baclofen . [Article]
7. Ertzgaard P, Campo C, Calabrese A: Efficacy and safety of oral baclofen in the management of spasticity: A rationale for intrathecal baclofen. J Rehabil Med. 2017 Mar 6;49(3):193-203. doi: 10.2340/16501977-2211. [Article]
8. Romito JW, Turner ER, Rosener JA, Coldiron L, Udipi A, Nohrn L, Tausiani J, Romito BT: Baclofen therapeutics, toxicity, and withdrawal: A narrative review. SAGE Open Med. 2021 Jun 3;9:20503121211022197. doi: 10.1177/20503121211022197. eCollection 2021. [Article]
9. Leung NY, Whyte IM, Isbister GK: Baclofen overdose: defining the spectrum of toxicity. Emerg Med Australas. 2006 Feb;18(1):77-82. doi: 10.1111/j.1742-6723.2006.00805.x. [Article]
10. Kochak GM, Rakhit A, Wagner WE, Honc F, Waldes L, Kershaw RA: The pharmacokinetics of baclofen derived from intestinal infusion. Clin Pharmacol Ther. 1985 Sep;38(3):251-7. doi: 10.1038/clpt.1985.167. [Article]
11. FDA Approved Drug Products: Gablofen (baclofen) for intrathecal injection [Link]
12. FDA Approved Drug Products: Lyvispah (baclofen) oral granules [Link]
13. FDA Approved Drug Products: FLEQSUVY (baclofen) oral suspension [Link]
14. Cayman Chemical: Baclofen MSDS [Link]
15. EMC Summary of Product Characteristics: Baclofen Oral Tablets [Link]

External Links

Human Metabolome Database

HMDB0014327

KEGG Drug

D00241

PubChem Compound

2284

PubChem Substance

46508181

ChemSpider

2197

BindingDB

24182

RxNav

1292

ChEBI

2972

ChEMBL

CHEMBL701

Therapeutic Targets Database

DAP000257

PharmGKB

PA448533

Guide to Pharmacology

GtP Drug Page

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Baclofen

Clinical Trials

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Manufacturers

• Medtronic inc
• Schwarz pharma inc
• Actavis totowa llc
• Caraco pharmaceutical laboratories ltd
• Impax laboratories inc
• Ivax pharmaceuticals inc sub teva pharmaceuticals usa
• Lannett holdings inc
• Matrix laboratories ltd
• Mylan pharmaceuticals inc
• Northstar healthcare holdings ltd
• Teva pharmaceuticals usa inc
• Usl pharma inc
• Vintage pharmaceuticals inc
• Watson laboratories inc
• Novartis pharmaceuticals corp

Packagers

• Actavis Group
• Advanced Pharmaceutical Services Inc.
• Aidarex Pharmacuticals LLC
• Alphapharm Party Ltd.
• Amerisource Health Services Corp.
• Apotheca Inc.
• A-S Medication Solutions LLC
• Bryant Ranch Prepack
• Caraco Pharmaceutical Labs
• Cardinal Health
• Caremark LLC
• Comprehensive Consultant Services Inc.
• Corepharma LLC
• Direct Dispensing Inc.
• Dispensing Solutions
• Diversified Healthcare Services Inc.
• Genpharm LP
• Heartland Repack Services LLC
• Innoviant Pharmacy Inc.
• Ivax Pharmaceuticals
• Keltman Pharmaceuticals Inc.
• Lake Erie Medical and Surgical Supply
• Lannett Co. Inc.
• Major Pharmaceuticals
• Mckesson Corp.
• Medisca Inc.
• Medtronic
• Murfreesboro Pharmaceutical Nursing Supply
• Mylan
• Northstar Rx LLC
• Novartis AG
• Nucare Pharmaceuticals Inc.
• Palmetto Pharmaceuticals Inc.
• PD-Rx Pharmaceuticals Inc.
• Pharmaceutical Packaging Center
• Physicians Total Care Inc.
• Piramal Healthcare
• Preferred Pharmaceuticals Inc.
• Prepak Systems Inc.
• Prescription Dispensing Service Inc.
• Qualitest
• Rebel Distributors Corp.
• Remedy Repack
• Resource Optimization and Innovation LLC
• Sandhills Packaging Inc.
• Southwood Pharmaceuticals
• St Mary's Medical Park Pharmacy
• Stat Rx Usa
• UDL Laboratories
• United Research Laboratories Inc.
• USL Pharma Inc.
• Vangard Labs Inc.
• Vintage Pharmaceuticals Inc.
• Watson Pharmaceuticals

Dosage Forms

Prices

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US6221392	No	2001-04-24	2018-04-09
US6024981	No	2000-02-15	2018-04-09
US10610502	No	2020-04-07	2039-08-30
US10792262	No	2020-10-06	2039-07-29
US11324696	No	2017-09-29	2037-09-29
US11446246	No	2017-09-08	2037-09-08
US11491125	No	2021-09-29	2041-09-29
US11654124	No	2019-07-29	2039-07-29
US11850225	No	2021-09-29	2041-09-29
US11931328	No	2019-07-29	2039-07-29

State

Solid

Experimental Properties

Predicted Properties

Predicted ADMET Features

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Mass Spec (NIST)

Not Available

Spectra

Chromatographic Properties

Collision Cross Sections (CCS)

Targets

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Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Agonist

General Function

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:9872316, PubMed:9872744). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10075644, PubMed:10773016, PubMed:24305054). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644, PubMed:10773016, PubMed:10906333, PubMed:9872744). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:22660477, PubMed:9872744). Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:10075644, PubMed:22660477, PubMed:9872316, PubMed:9872744). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable)

Specific Function

G protein-coupled GABA receptor activity

Gene Name

GABBR2

Uniprot ID

O75899

Uniprot Name

Gamma-aminobutyric acid type B receptor subunit 2

Molecular Weight

105820.52 Da

References

1. Braun M, Wendt A, Buschard K, Salehi A, Sewing S, Gromada J, Rorsman P: GABAB receptor activation inhibits exocytosis in rat pancreatic beta-cells by G-protein-dependent activation of calcineurin. J Physiol. 2004 Sep 1;559(Pt 2):397-409. Epub 2004 Jul 2. [Article]
2. Bowery NG: GABAB receptor pharmacology. Annu Rev Pharmacol Toxicol. 1993;33:109-47. [Article]
3. Filippov AK, Couve A, Pangalos MN, Walsh FS, Brown DA, Moss SJ: Heteromeric assembly of GABA(B)R1 and GABA(B)R2 receptor subunits inhibits Ca(2+) current in sympathetic neurons. J Neurosci. 2000 Apr 15;20(8):2867-74. [Article]
4. Lehmann A: GABAB receptors as drug targets to treat gastroesophageal reflux disease. Pharmacol Ther. 2009 Jun;122(3):239-45. doi: 10.1016/j.pharmthera.2009.02.008. Epub 2009 Mar 19. [Article]
5. Martin SC, Russek SJ, Farb DH: Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1. Mol Cell Neurosci. 1999 Mar;13(3):180-91. [Article]
6. Pittman QJ: The action is at the terminal. J Physiol. 1999 Nov 1;520 Pt 3:629. [Article]
7. Fu Z, Yang H, Xiao Y, Zhao G, Huang H: The gamma-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens. Behav Brain Funct. 2012 Jul 10;8:20. doi: 10.1186/1744-9081-8-20. [Article]
8. Chen K, Li HZ, Ye N, Zhang J, Wang JJ: Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro. Brain Res Bull. 2005 Oct 30;67(4):310-8. doi: 10.1016/j.brainresbull.2005.07.004. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Allosteric modulator

General Function

Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:24912431, PubMed:28978524). Involved in the AKT signaling cascade (PubMed:24912431). Plays a role in regulation of cell migration, e.g. during wound healing (PubMed:28978524). Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels (PubMed:20228059). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival (By similarity)

Specific Function

actin binding

Gene Name

CXCR4

Uniprot ID

P61073

Uniprot Name

C-X-C chemokine receptor type 4

Molecular Weight

39745.055 Da

References

1. Guyon A, Kussrow A, Olmsted IR, Sandoz G, Bornhop DJ, Nahon JL: Baclofen and other GABAB receptor agents are allosteric modulators of the CXCL12 chemokine receptor CXCR4. J Neurosci. 2013 Jul 10;33(28):11643-54. doi: 10.1523/JNEUROSCI.6070-11.2013. [Article]
2. de Beaurepaire R: A Review of the Potential Mechanisms of Action of Baclofen in Alcohol Use Disorder. Front Psychiatry. 2018 Oct 17;9:506. doi: 10.3389/fpsyt.2018.00506. eCollection 2018. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Agonist

General Function

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:36103875, PubMed:9872316, PubMed:9872744). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10075644, PubMed:10773016, PubMed:10906333, PubMed:24305054, PubMed:9872744). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:9844003). Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:10075644, PubMed:22660477, PubMed:9844003, PubMed:9872316, PubMed:9872744). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen (PubMed:24305054, PubMed:9844003, PubMed:9872316)

Specific Function

extracellular matrix protein binding

Gene Name

GABBR1

Uniprot ID

Q9UBS5

Uniprot Name

Gamma-aminobutyric acid type B receptor subunit 1

Molecular Weight

108319.4 Da

References

1. Bowery NG: GABAB receptor pharmacology. Annu Rev Pharmacol Toxicol. 1993;33:109-47. [Article]
2. Garcia-Gil L, de Miguel R, Romero J, Perez A, Ramos JA, Fernandez-Ruiz JJ: Perinatal delta9-tetrahydrocannabinol exposure augmented the magnitude of motor inhibition caused by GABA(B), but not GABA(A), receptor agonists in adult rats. Neurotoxicol Teratol. 1999 May-Jun;21(3):277-83. [Article]
3. Lehmann A: GABAB receptors as drug targets to treat gastroesophageal reflux disease. Pharmacol Ther. 2009 Jun;122(3):239-45. doi: 10.1016/j.pharmthera.2009.02.008. Epub 2009 Mar 19. [Article]
4. Motalli R, Louvel J, Tancredi V, Kurcewicz I, Wan-Chow-Wah D, Pumain R, Avoli M: GABA(B) receptor activation promotes seizure activity in the juvenile rat hippocampus. J Neurophysiol. 1999 Aug;82(2):638-47. [Article]
5. Mott DD, Li Q, Okazaki MM, Turner DA, Lewis DV: GABAB-Receptor-mediated currents in interneurons of the dentate-hilus border. J Neurophysiol. 1999 Sep;82(3):1438-50. [Article]
6. Ogasawara T, Itoh Y, Tamura M, Mushiroi T, Ukai Y, Kise M, Kimura K: Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105, a cognition enhancer. Pharmacol Biochem Behav. 1999 Sep;64(1):41-52. [Article]
7. Pittman QJ: The action is at the terminal. J Physiol. 1999 Nov 1;520 Pt 3:629. [Article]
8. Stringer JL, Lorenzo N: The reduction in paired-pulse inhibition in the rat hippocampus by gabapentin is independent of GABA(B) receptor receptor activation. Epilepsy Res. 1999 Feb;33(2-3):169-76. [Article]
9. Fu Z, Yang H, Xiao Y, Zhao G, Huang H: The gamma-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens. Behav Brain Funct. 2012 Jul 10;8:20. doi: 10.1186/1744-9081-8-20. [Article]
10. Chen K, Li HZ, Ye N, Zhang J, Wang JJ: Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro. Brain Res Bull. 2005 Oct 30;67(4):310-8. doi: 10.1016/j.brainresbull.2005.07.004. [Article]
11. Omari TI, Benninga MA, Sansom L, Butler RN, Dent J, Davidson GP: Effect of baclofen on esophagogastric motility and gastroesophageal reflux in children with gastroesophageal reflux disease: a randomized controlled trial. J Pediatr. 2006 Oct;149(4):468-74. doi: 10.1016/j.jpeds.2006.05.029. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 11, 2024 10:52