In spastic patients, suprasegmental lesions interfere with descending control of interneuronal systems in the spinal cord. A better understanding of neurotransmitters and neuromodulators active in these interneuronal circuits has been the basis for pharmacological manipulation of spasticity (see Chapter 2 for further details). One of the most powerful drugs and certainly the most widely used in the past 30 years has been baclofen. Baclofen (4-amino-3-[p-chlorophenyl]-GABA) was initially developed as an antiepileptic medication. It did not prove to be very effective in this indication, and later studies actually suggested a possible procomitial action (1,2). However, during its clinical evaluation, baclofen was noted to reduce spasticity. Numerous clinical-efficacy studies were conducted in the 1970s, and after that the interest became mostly oriented towards a comparison with the newly available tizanidine in the 1980s. At the same time, several studies addressed the mechanisms of action of baclofen, both at the cellular and spinal-tissue levels. In this chapter, we will first review the chemistry and cellular mechanisms of action, the physiologic effect at the spinal-cord level, and the pharmacokinetics of baclofen. We will thereafter consider the clinical effects on spastic patients, and summarize a systematic review of published studies of patients with a variety of neurological disorders since the drug became available in 1966. We will also describe the possible side and toxic effects of baclofen, and finally present a recommended schedule of administration in different patient populations. Intrathecal baclofen (ITB) is discussed in Chapter 15.
KeywordsMultiple Sclerosis Spinal Cord Injury Amyotrophic Lateral Sclerosis Cerebral Palsy Intrathecal Baclofen
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