Baclofen (Lioresal) was introduced in 1967 as an oral medication for the treatment of muscle spasticity. While the drug can readily be absorbed from the gut into the bloodstream when taken orally, it has great difficulty in getting to the target site within the spinal cord. This is because of the existence of a barrier which isolates the nervous system from the rest of the body, the so-called blood-brain barrier.
The purpose of this barrier is to protect the nervous system and its functioning from substances circulating throughout the rest of the body, including drugs circulating in the bloodstream. To obtain an adequate concentration of the drug at the sites within the spinal cord where it works, very high concentrations must be circulating within the blood so as to push the drug down a concentration gradient from the blood across the barrier into the central nervous system.
These high concentrations within the blood compartment cause undesired side effects, such as muscle fatigue, which limit the usefulness of the drug when taken orally. Consequently, the drug has proven useful only in those few who obtain the desired relaxation of their muscle spasticity at lower doses of the medication. It was for this reason that physicians investigated administering the drug directly into the cerebrospinal fluid (CSF).