| Item |
Information |
|
Drug Groups
|
approved |
|
Description
|
Baclofen is a gamma-amino-butyric acid (GABA) derivative used as a skeletal muscle relaxant. Baclofen stimulates GABA-B receptors leading to decreased frequency and amplitude of muscle spasms. It is especially useful in treating muscle spasticity associated with spinal cord injury. It appears to act primarily at the spinal cord level by inhibiting spinal polysynaptic afferent pathways and, to a lesser extent, monosynaptic afferent pathways. |
| Indication |
For the alleviation of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. |
| Pharmacology |
Baclofen is a muscle relaxant and antispastic. Baclofen is useful for the alleviation of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. 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. In studies with animals, Baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression. 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 intersubject variation in absorption and/or elimination. |
| Toxicity |
LD50=45 mg/kg (male mice, IV); LD50=78 mg/kg (male rat, IV) |
| Affected Organisms |
| • |
Humans and other mammals |
|
| Biotransformation |
~ 15% of the dose is metabolized in the liver, primarily by deamination. 70-80% of the dose is excreted unchanged or as metabolites in urine and the remainder is excreted in feces. |
| Absorption |
Rapidly and almost completely absorbed from the GI tract. |
| Half Life |
2.5-4 hours |
| Protein Binding |
30% |
| Elimination |
In a study using radiolabeled baclofen, approximately 85% of the dose was excreted unchanged in the urine and feces.
Baclofen is excreted primarily by the kidney as unchanged drug; 70 - 80% of a dose appears in the urine as unchanged drug. The remainder is excreted as unchanged drug in the feces or as metabolites in the urine and feces. |
| Distribution |
* 59 L |
| Clearance |
* 180 mL/min |
| References |
| • |
Dzitoyeva S, Dimitrijevic N, Manev H: Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5485-90. Epub 2003 Apr 11.
[Pubmed]
|
| • |
Mezler M, Muller T, Raming K: Cloning and functional expression of GABA(B) receptors from Drosophila. Eur J Neurosci. 2001 Feb;13(3):477-86.
[Pubmed]
|
| • |
See S, Ginzburg R: Skeletal muscle relaxants. Pharmacotherapy. 2008 Feb;28(2):207-13.
[Pubmed]
|
|
| External Links |
|