General
Preferred name
BACLOFEN
Synonyms
BACLOFEN HYDROCHLORIDE (+/-) ()
Benzenepropanoic acid, .beta.-(aminomethyl)-4-chloro- ()
(±)-Baclofen ()
S(-)-BACLOFEN ()
Lioresal ()
Baclofen, (S)(+) ()
Baclofen, (R)(-) ()
(RS)-Baclofen ()
Baclofen (R,S) ()
(+-)-Baclofen ()
Gablofen ()
Kemstro ()
BA-34,647 ()
Fleqsuvy ()
Ozobax ()
Lioresal Intrath ()
Lyvispah ()
NSC-755906 ()
Lyflex ()
BA-34647 ()
Baclospas-10 ()
?(±)-Baclofen? ()
(±)-Baclofen-d4 ()
P&D ID
PD002799
CAS
70206-22-3
1134-47-0
62594-36-9
28311-31-1
1189938-30-4
Tags
natural product
drug
available
Approved by
FDA
First approval
1977
Drug Status
approved
Drug indication
Fragile X syndrome
Relaxant (muscle)
Multiple sclerosis
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE
Elimination half-life: Approximately 5.5 hours [FDA label].
PHARMACODYNAMICS
In neurological diseases associated with spasm of the skeletal muscles, the clinical effects of baclofen occur due to baclofen action on reflex muscle contractions and of significant relief from painful spasm, automatism, as well as clonus. Baclofen, when used as indicated, improves mobility, increasing levels of independence, and facilitates both passive and active physiotherapy. Baclofen also stimulates gastric acid secretion [F2980]. GABA-B receptor activation by baclofen may produce protective neurological effects. Baclofen also possesses anti-inflammatory properties that may be of interest in the study of addiction treatment [A173938]. Preclinical studies have shown that GABA-B receptors have roles in memory storage and retrieval, reward, motivation, mood, as well as anxiety. Neuroimaging studies in humans indicate that baclofen produces region-specific alterations in brain activity.
MOA
The exact mechanism of action of baclofen is not fully understood at this time [FDA label], [F2983]. Many studies indicate that baclofen is a GABA-B receptor agonist [A25184], [A173923], [A173926], [A254], [A173929]. Despite this, there is no conclusive evidence that effects of baclofen on GABA systems are involved in the production of its clinical effects [FDA label]. Baclofen is an effective and widely used antispastic agent with a spinal site of action. Its mechanism of action and pharmacological properties are different from the effects of other antispastic agents. In addition, baclofen has central sites of action, shown by its adverse event profile and general CNS depressant properties [F2980]. GABA-B receptors interact with signal transduction pathways and neurotransmitter systems. Baclofen exerts an antinociceptive effect. The clinical significance of this warrants further research data for clarification. Baclofen depresses monosynaptic and polysynaptic reflex transmission, by various actions, and possibly including the stimulation of GABAβ-receptors. This stimulation results in the inhibition of excitatory neurotransmitter (glutamate and aspartate) release, which may normally contribute to pain and spasticity[F2980]. Although baclofen is an analog of the inhibitory neurotransmitter gamma-amino-butyric acid (GABA), there are no conclusive data indicating GABA systems are involved in its clinical effects [FDA label].
ROE
Baclofen is rapidly and extensively eliminated from the body. There is significant intersubject variation in elimination rates. Baclofen is excreted mainly by the kidney as unchanged drug. Seventy to eighty (70 - 80%) of a dose is measured in the urine as unchanged drug. The remainder of the dose is excreted as unchanged drug in the feces or as metabolites in the urine and feces. Excretion is complete within 72 hours after administration [FDA label].
INDICATION
Baclofen is administered for the relief of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and associated pain and clonus, in addition to muscular rigidity [FDA label]. Patients receiving this drug should have reversible spasticity for baclofen to promote the restoration of residual function. This drug is not indicated in the treatment of skeletal muscle spasm caused by rheumatic disorders. The efficacy of baclofen in stroke, cerebral palsy, and Parkinson's disease has not been determined and, therefore, baclofen is not recommended for these conditions [FDA label].
TOXICITY
LD50 after oral administration in rats: 145 mg/kg [MSDS] **Overdosage**: Vomiting, muscular hypotonia, drowsiness, accommodation disorders, coma, respiratory depression, and seizures may occur with overdosage [FDA label]. **Pregnancy**: This drug is a pregnancy category C drug. There are no adequate and well-controlled studies that have been performed with pregnant women. Baclofen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [FDA label]. **Excretion in breastmilk**: It is unknown whether this drug is excreted in human breast milk. Because many drugs are excreted in human milk, caution is warranted when baclofen is administered to a nursing woman [FDA label].
METABOLISM
Approximately 15% of the dose is metabolized in the liver, mainly by deamination [FDA label]. In a clinical study with radiolabeled baclofen, approximately 85% of the dose was excreted unchanged in the urine and feces. The γ-hydroxy metabolite, 3-(p-chlorophenyl)-4-hydroxybutyric acid, is produced after the deamination of baclofen [FDA label]. Because baclofen is partially metabolized in the liver, patients with impaired liver function should be regularly monitored with liver function tests [F2980].
ABSORPTION
Rapidly and almost completely absorbed from the gastrointestinal tract. Absorption may be dose-dependent, being reduced with increased doses [FDA label]. Baclofen, when introduced directly into the intrathecal space, allows for effective CSF concentrations to be achieved with resulting plasma concentrations 100 times less than concentrations occurring with oral administration [F2983], [FDA label].
MOA
The exact mechanism of action of baclofen is not fully understood at this time [FDA label], [F2983]. Many studies indicate that baclofen is a GABA-B receptor agonist [A254], [A25184], [A173923], [A173926], [A173929]. Despite this, there is no conclusive evidence that the effects of baclofen on GABA systems are involved in the production of its clinical effects [FDA label]. ; ; Baclofen is an effective and widely used antispastic agent with a spinal site of action. Its mechanism of action and pharmacological properties are different from the effects of other antispastic agents. In addition, baclofen has central sites of action, shown by its adverse event profile and general CNS depressant properties [F2980]. GABA-B receptors interact with signal transduction pathways and neurotransmitter systems. Baclofen exerts an antinociceptive effect. The clinical significance of this warrants further research data for clarification. ; ; Baclofen depresses monosynaptic and polysynaptic reflex transmission, by various actions, and possibly including the stimulation of GABAβ-receptors. This stimulation results in the inhibition of excitatory neurotransmitter (glutamate and aspartate) release, which may normally contribute to pain and spasticity[F2980]. Although baclofen is an analog of the inhibitory neurotransmitter gamma-amino-butyric acid (GABA), there are no conclusive data indicating GABA systems are involved in its clinical effects [FDA label].
PHARMACODYNAMICS
In neurological diseases associated with spasm of the skeletal muscles, the clinical effects of baclofen occur due to baclofen action on reflex muscle contractions and of significant relief from painful spasm, automatism, as well as clonus. Baclofen, when used as indicated, improves mobility, increasing levels of independence, and facilitates both passive and active physiotherapy. Baclofen also stimulates gastric acid secretion [F2980].; ; GABA-B receptor activation by baclofen may produce protective neurological effects. Baclofen also possesses anti-inflammatory properties that may be of interest in the study of addiction treatment [A173938]. Preclinical studies have shown that GABA-B receptors have roles in memory storage and retrieval, reward, motivation, mood, as well as anxiety. Neuroimaging studies in humans indicate that baclofen produces region-specific alterations in brain activity.
INDICATION
Baclofen is administered for the relief of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and associated pain and clonus, in addition to muscular rigidity [FDA label].; ; Patients receiving this drug should have reversible spasticity for baclofen to promote the restoration of residual function. This drug is not indicated in the treatment of skeletal muscle spasm caused by rheumatic disorders. The efficacy of baclofen in stroke, cerebral palsy, and Parkinson's disease has not been determined and, therefore, baclofen is not recommended for these conditions [FDA label].;
TOXICITY
LD50 after oral administration in rats: 145 mg/kg [MSDS]; ; **Overdosage**: Vomiting, muscular hypotonia, drowsiness, accommodation disorders, coma, respiratory depression, and seizures may occur with overdosage [FDA label].; ; **Pregnancy**: This drug is a pregnancy category C drug. There are no adequate and well-controlled studies that have been performed with pregnant women. Baclofen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [FDA label].; ; **Excretion in breastmilk**: It is unknown whether this drug is excreted in human breast milk. Because many drugs are excreted in human milk, caution is warranted when baclofen is administered to a nursing woman [FDA label].
METABOLISM
Approximately 15% of the dose is metabolized in the liver, mainly by deamination [FDA label].; ; In a clinical study with radiolabeled baclofen, approximately 85% of the dose was excreted unchanged in the urine and feces. The γ-hydroxy metabolite, 3-(p-chlorophenyl)-4-hydroxybutyric acid, is formed by the deamination of baclofen [FDA label].; ; Because baclofen is partially metabolized in the liver, patients with impaired liver function should be regularly monitored with liver function tests [F2980].
ABSORPTION
Rapidly and almost completely absorbed from the gastrointestinal tract. Absorption may be dose-dependent, being reduced with increased doses [FDA label].; ; Baclofen, when introduced directly into the intrathecal space, allows for effective CSF concentrations to be achieved with resulting plasma concentrations 100 times less than concentrations occurring with oral administration [F2983], [FDA label].
DESCRIPTION
The approved drug baclofen is a racemic mixture of two enantiomers; (R)-baclofen and (S)-baclofen. We show the non-stereo structure to represent the mixture.
(GtoPdb)
DESCRIPTION
GABA-B receptor agonist; antispastic agent; muscle relaxant
(LOPAC library)
DESCRIPTION
alpha2 agonist
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
2
Compound Sets
32
AdooQ Bioactive Compound Library
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
JUMP-Target 1 Compound Set
Ki Database
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
54
Molecular Weight
213.06
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
2
Rotatable Bonds
4
Ring Count
1
Aromatic Ring Count
1
cLogP
1.86
TPSA
63.32
Fraction CSP3
0.3
Chiral centers
1.0
Largest ring
6.0
QED
0.8
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Selectivity
GABA-B
MOA
metabotropic GABA receptor agonist
GABA Receptor agonist
Agonist
GABA(B) Agonists
Target
GABA-B Receptor
GABAR
KCTD16
GABA Receptor
Pathway
Membrane Transporter/Ion Channel
Neuroscience
Neuronal Signaling
Primary Target
GABAB Receptors
Member status
member
Therapeutic Class
Muscle Relaxants
Source data
