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.

mechanism of action

Baclofen is a direct agonist at GABAB 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.

toxicity

LD₅₀=45 mg/kg (male mice, IV); LD₅₀=78 mg/kg (male rat, IV)

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

route of 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.