What is baclofen

[galen]

My doctor just put me on baclofen 5mg 3 times a day because all the tingleing and stiffness in my legs keeps me up at night. It says in big letters on the bottle take only as directed and do not stop without consulting with your doctor. What exactly is baclofen? My doctor is not good at explaining this stuff. When I go see him and tell him about my pain, etc. I feel like he doesn't really care. Thanks. Galen

[Wise Young]

Galen, baclofen is a GABA-B agonist. What does this mean? The main inhibitory neurotransmitter in the central nervous system is a amino acid called gamma aminobutyric acid (GABA). GABA affects neurons by affecting at least three receptors: GABA-A, GABA-B, and GABA-C.

GABA-A receptors are believed to mediate the inhibitory effects of GABA on neurons; it opens chloride channels on membrages. When these channels open, the neuronal membrane potential becomes more negative (hyperpolarize) while excitatory neurotransmitters bring the neurons closer to activation threshold (depolarize). Almost all excitatory activity in neurons is associated with inhibitory activity that limit the excitation. GABA-A receptor antagonists (blockers) increase the excitability of the central nervous system and can cause seizures. Two toxins are known to block GABA-A receptors selectively: picrotoxin and bicucullin. Both of these cause seizures when they are given in high doses.

GABA-B receptors affect neurons through a very different mechanism. They turn on intracellular messengers that may result in longer term decrease of excitability of neurons. GABA-B receptor activation may also result in more GABA being produced in the nervous system, increased sensitivity to GABA-A receptor activation, etc. Baclofen is a GABA-B agonist, meaning that they turn on GABA-B receptors. The effects of GABA-B, however, are complex because they may affect certain neurons more than others.

GABA-C receptors are similar to GABA-A receptors except that they do not respond to picrotoxin or bicuculline.

Baclofen tends to reduce the hyperexcitability on neurons in the spinal cord that contribute to spasticity and allodynia. Allodynia is hypersensitivity to touch and is the sensory counterpart to spasticity. The effects of baclofen depend on dose. At moderate doses, it reduces both spasticity and allodynia. However, in high doses, it will dramatically reduce excitability of the nervous system, producing flaccidity and depressed reflexes. It also enhances inhibitory circuits in the brain. Baclofen overdoses can cause unconsciousness, can reduce energy, can increase fatigue, and can even produce coma.

Most people take baclofen by mouth. However, at doses exceeding 100 mg per day, the drug may have unacceptable side effects on the brain. People may have different sensitivity to baclofen. For people who require more than 100 mg of baclofen per day and who have unacceptable side-effects of baclfoen, the drug can be delivered intrathecally (directly to the spinal cord through a catheter that is inserted inside the dura to drip the drug directly onto the spinal cord). Intrathecal baclofen can achieve higher baclofen levels in the spinal cord with less effect on the brain.

In general, I believe that the dose of baclofen be titrated so that it suppresses but does not eliminate spasticity. Spasticity results in muscle activity that prevents atrophy.

Wise.

PS 5 mg three times a day is a relatively low dose.

[galen]

Thank you Dr.Wise. It seems like even at this low dosage I am able to sleep better at night. I am able to walk some with a walker and afo's and I do not want to take anything that may reduce my ability to do this. Galen