Posted by hub (209.183.121.192) on December 13, 2000 at 12:42:47:
In Reply to: Baclofen posted by Stephen on December 13, 2000 at 11:56:51:
Description: Baclofen is an oral skeletal muscle relaxant. It is a derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Clinically, baclofen is used to treat spasticity and improve mobility in patients with multiple sclerosis and other spinal cord lesions by decreasing the number and severity of spasms and relieving associated pain, clonus, and muscle rigidity. Baclofen also improves bowel and bladder function in some of these patients. Baclofen was approved by the FDA in November 1977. On February 28, 1995, the FDA granted approval under a treatment IND to study intrathecal baclofen for the treatment of spasticity of cerebral origin. L-baclofen is designated an orphan drug for treatment of trigeminal neuralgia.
Mechanism of Action: Baclofen's mechanism of action is not fully understood, but it is believed that the drug works mainly at the level of the spinal cord to block polysynaptic afferent pathways and, to a lesser extent, monosynaptic afferent pathways. Baclofen may inhibit the transmission of impulses through these pathways by acting as an inhibitory neurotransmitter itself or by hyperpolarizing the primary afferent nerve terminals, which inhibits the release of excitatory neurotransmitters such as glutamate and aspartic acids. Because large doses of baclofen cause CNS depression, it is postulated that the drug works at supraspinal sites as well. One reference describes baclofen as a GABA agonist. This leads to a decreased release of the neurotransmitters aspartate and glutamate and decreased excitatory input into alpha-motor neurons.
Pharmacokinetics: Baclofen is administered orally and is rapidly and almost completely absorbed, although bioavailability varies from patient to patient. Both the rate and extent of absorption is inversely proportional to the dose. Peak blood concentrations are achieved within 2—3 hours.
Baclofen is distributed throughout the body but only minimally crosses the blood-brain barrier. Protein binding is low. About 15% of a dose is metabolized by the liver. The half-life ranges from 2.5—4 hours. The kidney excretes 70—85% of a dose as unchanged drug and metabolites, and the remainder is excreted via the feces.