BACLOFEN

Details

Stereochemistry	RACEMIC
Molecular Formula	C10H12ClNO2
Molecular Weight	213.6611
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cc(ccc1C(CC(=O)O)CN)Cl

InChI

InChIKey=KPYSYYIEGFHWSV-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022462s000lbl.pdf
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18221197 https://www.ncbi.nlm.nih.gov/pubmed/15486423

Baclofen (brand names Kemstro, Lioresal, and Gablofen) is a derivative of gamma-aminobutyric acid (GABA). Baclofen is a muscle relaxer and an antispastic agent and is used to treat muscle symptoms caused by multiple sclerosis, including spasm, pain, and stiffness. It is primarily used to treat spasticity and is under investigation for the treatment of alcoholism. Although baclofen is an analog of the putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA), there is no conclusive evidence that actions on GABA systems are involved in the production of its clinical effects. Baclofen is rapidly and extensively absorbed and eliminated. Absorption may be dose-dependent, being reduced with increasing doses. Baclofen is excreted primarily by the kidney in unchanged form and there is relatively large intersubjective variation in absorption and/or elimination. Baclofen is a direct agonist at GABA-B receptors. The precise mechanism of action of baclofen is not fully known. It is capable of inhibiting both monosynaptic and polysynaptic reflexes at the spinal level, possibly by hyperpolarization of afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-B receptor 27 Target ID: CHEMBL2111463 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8388192	Agonist 2470

Conditions

Condition	Modality	Targets	Highest Phase	Product
Spasticity 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022462s000lbl.pdf	Primary		Approved 8043	GABLOFEN Approved Use Gablofen (baclofen injection) is indicated for use in the management of severe spasticity in adult and pediatric patients age 4 years and above. Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. For spasticity of spinal cord origin, chronic infusion of Gablofen via an implantable pump should be reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable CNS side effects at effective doses. Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal baclofen therapy. Gablofen is intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, only with the Medtronic SynchroMed® II Programmable Pump or other pumps labeled for intrathecal administration of Gablofen Launch Date 1.29012479E12

C_max

Value	Dose	Co-administered	Analyte	Population
0.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2336342/	10 mg 4 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		BACLOFEN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
178 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21589_kemstro_lbl.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		BACLOFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2336342/	10 mg 4 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		BACLOFEN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.75 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21589_kemstro_lbl.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		BACLOFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21589_kemstro_lbl.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		BACLOFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg 1 times / day single, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: single Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021589s000_Kemstro_MedR.pdf Page: nda/2003/021589s000_Kemstro_MedR.pdf - p.36	healthy, 25 years n = 1 Health Status: healthy Age Group: 25 years Sex: F Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021589s000_Kemstro_MedR.pdf Page: nda/2003/021589s000_Kemstro_MedR.pdf - p.36	Other AEs: Hypertension, Respiratory depression... Other AEs: Hypertension Respiratory depression Coma Hypotonia Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021589s000_Kemstro_MedR.pdf Page: nda/2003/021589s000_Kemstro_MedR.pdf - p.36
800 mg 1 times / day single, oral Studied dose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021589s000_Kemstro_MedR.pdf https://pubmed.ncbi.nlm.nih.gov/9711203/	unhealthy, 42 years n = 1 Health Status: unhealthy Condition: spasticity Age Group: 42 years Sex: M Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021589s000_Kemstro_MedR.pdf https://pubmed.ncbi.nlm.nih.gov/9711203/	Other AEs: Hypotension... Other AEs: Hypotension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021589s000_Kemstro_MedR.pdf https://pubmed.ncbi.nlm.nih.gov/9711203/
800 mg 1 times / day single, oral Studied dose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021589s000_Kemstro_MedR.pdf Page: nda/2003/021589s000_Kemstro_MedR.pdf - p.36	unhealthy, 42 years n = 1 Health Status: unhealthy Condition: spasticity Age Group: 42 years Sex: M Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021589s000_Kemstro_MedR.pdf Page: nda/2003/021589s000_Kemstro_MedR.pdf - p.36	Other AEs: Hypotonia, Bradycardia... Other AEs: Hypotonia Bradycardia Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021589s000_Kemstro_MedR.pdf Page: nda/2003/021589s000_Kemstro_MedR.pdf - p.36
10 mg 3 times / day multiple, oral Recommended Dose: 10 mg, 3 times / day Route: oral Route: multiple Dose: 10 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3912190/	unhealthy, 69-81 years n = 12 Health Status: unhealthy Condition: stroke Age Group: 69-81 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/3912190/	Disc. AE: Drowsiness... AEs leading to discontinuation/dose reduction: Drowsiness (grade 3, 41.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/3912190/
30 mg 1 times / day multiple, oral Recommended Dose: 30 mg, 1 times / day Route: oral Route: multiple Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15597084/	unhealthy, mean age 42 years n = 12 Health Status: unhealthy Condition: alcohol dependence Age Group: mean age 42 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/15597084/	Disc. AE: Drowsiness, Fatigue... AEs leading to discontinuation/dose reduction: Drowsiness (grade 1-2, 16.7%) Fatigue (grade 1-2, 8.3%) Confusion (grade 1-2, 8.3%) Dizziness (grade 1-2, 8.3%) Insomnia (grade 1-2, 8.3%) Constipation (grade 1-2, 8.3%) Depression (grade 1-2, 8.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/15597084/
10 mg 3 times / day steady, oral Dose: 10 mg, 3 times / day Route: oral Route: steady Dose: 10 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01008280	unhealthy n = 88 Health Status: unhealthy Condition: Hepatitis C Population Size: 88 Sources: https://clinicaltrials.gov/ct2/show/NCT01008280	Other AEs: Confusion, Dizziness... Other AEs: Confusion (below serious, 20 patients) Dizziness (below serious, 23 patients) Drowsiness (below serious, 34 patients) Hallucinations (below serious, 5 patients) Headache (below serious, 22 patients) Hypotension (below serious, 7 patients) Itching (below serious, 13 patients) Loss of consciousness (below serious, 4 patients) Paresthesia (below serious, 11 patient) Rash (below serious, 8 patients) Slurred speech (below serious, 9 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01008280
10 mg 3 times / day steady, oral Dose: 10 mg, 3 times / day Route: oral Route: steady Dose: 10 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01751386	unhealthy n = 20 Health Status: unhealthy Condition: Alcoholism Population Size: 20 Sources: https://clinicaltrials.gov/ct2/show/NCT01751386	Other AEs: Increased appetite, Insomnia... Other AEs: Increased appetite (below serious, 1 patient) Insomnia (below serious, 3 patients) Depression (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01751386
10 mg 3 times / day steady, oral Dose: 10 mg, 3 times / day Route: oral Route: steady Dose: 10 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01980706	unhealthy n = 43 Health Status: unhealthy Condition: Alcohol Dependence Population Size: 43 Sources: https://clinicaltrials.gov/ct2/show/NCT01980706	Other AEs: Sedation, Dizziness... Other AEs: Sedation (below serious, 25 patients) Dizziness (below serious, 12 patients) Nausea (below serious, 5 patients) Constipation (below serious, 4 patients) Headache (below serious, 5 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01980706
30 mg 3 times / day steady, oral Dose: 30 mg, 3 times / day Route: oral Route: steady Dose: 30 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01980706	unhealthy n = 37 Health Status: unhealthy Condition: Alcohol Dependence Population Size: 37 Sources: https://clinicaltrials.gov/ct2/show/NCT01980706	Other AEs: Drowsiness, Sedation... Other AEs: Drowsiness (serious, 1 patient) Sedation (below serious, 20 patients) Dizziness (below serious, 8 patients) Headache (below serious, 4 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01980706

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2972	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2972
ChemicalBook	CB8669450	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8669450
MolPort	MolPort-002-051-370	https://www.molport.com/shop/molecule-link/MolPort-002-051-370
eMolecules	535235	https://www.emolecules.com/cgi-bin/more?vid=535235

PubMed

Title	Date	PubMed
Status epilepticus complicating intrathecal baclofen overdose.	1992 Feb 8	1346454
Effects of nitrendipine, chlordiazepoxide, flumazenil and baclofen on the increased anxiety resulting from alcohol withdrawal.	1992 Jan	1557510
Effects of some GABAergic agents on quinine-induced seizures in mice.	1992 Jul 15	1322322
A case of mania associated with high-dose baclofen therapy.	1992 Jun	1629392
Indication, efficiency and complications of intrathecal pump supported baclofen treatment in spinal spasticity.	1992 Jun	1442217
Prolonged seizure activity after baclofen withdrawal.	1992 Mar	1549245
[Baclofen intoxication in chronic hemodialysis and kidney transplantation].	1992 May 8	1576939
Death after acute withdrawal of intrathecal baclofen: case report and literature review.	1999 Dec	10597813
Effect of baclofen on cocaine self-administration in rats reinforced under fixed-ratio 1 and progressive-ratio schedules.	2000 Feb	10755745
Continuous intrathecal pump infusion of baclofen with antibiotic drugs for treatment of pump-associated meningitis. Case report.	2000 Feb	10659025
Involvement of GABAergic neurotransmission in the neurobiology of the apomorphine-induced aggressive behavior paradigm, a model of psychotic behavior in rats.	2000 Oct	11256236
Inhibition of baclofen on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity.	2001 Apr	11352538
GABA enhances transmission at an excitatory glutamatergic synapse.	2001 Aug 15	11487616
Cloning and functional expression of GABA(B) receptors from Drosophila.	2001 Feb	11168554
Modification of d-amphetamine-induced responses by baclofen in rats.	2001 Jan	11271399
Long-term intrathecal Baclofen infusion in supraspinal spasticity of adulthood.	2002 Feb	11903116
Baclofen decreases methamphetamine self-administration in rats.	2002 Jul 2	12151750
A possible baclofen-induced neurotoxicity in a CAPD patient who recovered with long-duration hemodialysis.	2002 Mar-Apr	11990422
Deep venous thrombosis as a result of hypotonia secondary to intrathecal baclofen therapy: a case report.	2002 Sep	12235615
Baclofen attenuates conditioned locomotion to cues associated with cocaine administration and stabilizes extracellular glutamate levels in rat nucleus accumbens.	2003	12676144
Pharmacological characterisation of a cell line expressing GABA B1b and GABA B2 receptor subunits.	2003 Apr 1	12663046
Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence.	2003 Apr 29	12692303
Lithium-induced periodic alternating nystagmus.	2003 Jan 28	12552061
Intrathecal baclofen for stiff-person syndrome: life-threatening intermittent catheter leakage.	2003 Jun 24	12821743
Intrathecal baclofen withdrawal mimicking sepsis.	2003 May	12745045
Pharmacological sensitivity and gene expression analysis of the tibial nerve injury model of neuropathic pain.	2003 May 30	12787826
Pharmacological complications of the chronic baclofen infusion in the severe spinal spasticity. Personal experience and review of the literature.	2004 Dec	15876986
Baclofen as adjunctive treatment for a patient with cocaine dependence and schizoaffective disorder.	2004 Oct	15349029
Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates.	2005 Feb	15630589
Different sensitivity to the motor incoordinating effects of gamma-hydroxybutyric acid (GHB) and baclofen in GHB-sensitive and GHB-resistant rats.	2005 Feb 1	15680346
Injections of baclofen into the ventral medial prefrontal cortex block the initiation, but not the expression, of cocaine sensitization in rats.	2005 Jul	15696327
Prolonged intrathecal baclofen withdrawal syndrome. Case report and discussion of current therapeutic management.	2005 Jun	16028775
Severe seizures during propofol induction in a patient with syringomyelia receiving baclofen.	2005 May	15845707
Intracerebral baclofen administration decreases amphetamine-induced behavior and neuropeptide gene expression in the striatum.	2005 May	15592348
[Baclofen-associated encephalopathy in a hemodialysis patient with hiccups].	2006	17058862
Intrathecal baclofen toxicity and deep coma in minutes.	2006	16859228
Cocaine-induced locomotor activity and Fos expression in nucleus accumbens are sensitized for 6 months after repeated cocaine administration outside the home cage.	2006 Aug	16930414
GABAB1 receptor subunit isoforms exert a differential influence on baseline but not GABAB receptor agonist-induced changes in mice.	2006 Dec	16990508
Differential effects of chronic amphetamine and baclofen administration on cAMP levels and phosphorylation of CREB in distinct brain regions of wild type and monoamine oxidase B-deficient mice.	2006 Dec 15	16983645
Antinociceptive and behavioral effects of ribavirin in mice.	2006 Feb	16563475
Aseptic meningitis after intrathecal baclofen injection.	2006 May	16172626
GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression.	2006 May 17	16707789
Baclofen-induced neurotoxicity in chronic renal failure patients with intractable hiccups.	2006 Nov	17195438
Baclofen-induced psychosis.	2006 Nov	17047139
Genomic and functional conservation of sedative-hypnotic targets in the zebrafish.	2007 Apr	17496723
GABA(B) receptor-positive modulation decreases selective molecular and behavioral effects of cocaine.	2007 Feb	16710312
Experience with external pump trial prior to implantation for intrathecal baclofen in ambulatory patients with spastic cerebral palsy.	2007 Jan-Mar	17418354

Patents

Sample Use Guides

In Vivo Use Guide

Gablofen is approved only for use with the Medtronic SynchroMed® II Programmable Pump or other pumps labeled 34 for intrathecal administration of Gablofen (baclofen injection). Lowest dose with an optimal response should be used, generally 300 to 800 mcg/day for spasticity of spinal cord origin and 90 to 700 mcg/day for spasticity of cerebral origin; Titrate Gablofen to maintain some degree of muscle tone and allow occasional spasms

Route of Administration: Other

In Vitro Use Guide

Unknown

Name

Type

Language

BACLOFEN

Official Name

English

KEMSTRO

Brand Name

English

BACLOFEN [JAN]

Common Name

English

BACLOFEN [USP MONOGRAPH]

Common Name

English

OZOBAX

Brand Name

English

BACLOFEN [MI]

Common Name

English

BA-34647

Code

English

BACLOFEN [USAN]

Common Name

English

BACLOFEN [WHO-DD]

Common Name

English

BACLOFEN [ORANGE BOOK]

Common Name

English

BACLOFEN [USP-RS]

Common Name

English

4-AMINO-3-(4-CHLOROPHENYL)BUTANOIC ACID

Systematic Name

English

BACLOFEN [INN]

Common Name

English

BACLOFEN [MART.]

Common Name

English

GABLOFEN

Brand Name

English

BUTANOIC ACID, 4-AMINO-3-(4-CHLOROPHENYL)-

Common Name

English

BA-34,647

Code

English

BACLOFEN [EP MONOGRAPH]

Common Name

English

NSC-755906

Code

English

BACLOFEN [VANDF]

Common Name

English

(RS)-BACLOFEN

Common Name

English

LIORESAL

Brand Name

English

.BETA.-(AMINOMETHYL)-P-CHLOROHYDROCINNAMIC ACID

Common Name

English

Classification Tree Code System Code

WHO-ATC

M03BX01