Intrathecal administration of 4-aminopyridine in chronic spinal injured patients

ABSTRACT STUDY DESIGN: Intrathecal administration of 4-aminopyridine (4-AP) in chronic spinal cord injured (SCI) patients. OBJECTIVE: To determine the safety and effects of intrathecal

administration of 4-AP in a small population of chronic SCI patients. SETTING: The post anesthesia care unit of a tertiary care hospital. METHODS: Following animal mode studies to establish

dosing safety, six subjects with chronic SCI were examined. In each subject, an intrathecal catheter was placed with the tip as close to the lesion level as possible. 4-AP was infused at 5 

μg/h for a period of 4–5 h. Vital signs were recorded and sensory-motor physical examinations and pain questionnaires were administered for 24 h. In two patients, samples of cerebrospinal

fluid for analysis were drawn from a second intrathecal catheter. RESULTS: No adverse systemic side effects were noted. One patient showed transient improvement in sensory function; two

showed transient increases in spasticity; three showed transient increases in cutaneomuscular reflexes and two showed an apparent small increase in volitional motor control. The

concentration of 4-aminopyridine in the cerebrospinal fluid reached a peak of 163 ng/ml at 4 h in one subject and 122 ng/ml at 5 h in the other subject examined. CONCLUSION: Intrathecal

administration of 4-aminopyridine at a rate of 5 μg/h does not appear to cause adverse effects and may modify spinal cord function. This route of administration allows local cerebrospinal

fluid concentrations equivalent to those produced by maximum tolerable systemic doses, which require 1000 times more drug substance to be delivered to the subject as a whole. Intrathecal

administration offers the potential to focus therapeutic effects to the lesion site while minimizing systemic side effects. SIMILAR CONTENT BEING VIEWED BY OTHERS PHARMACOLOGIC THERAPIES OF

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AFFILIATIONS * Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas, USA JA Halter * Department of Anesthesiology, Baylor College of Medicine,

Houston, Texas, USA O Calvillo * Institute for Rehabilitation and Research, Houston, Texas, USA WH Donovan * Department of Physical Medicine and Rehabilitation, University of Texas Houston

Medical School, Houston, Texas, USA WH Donovan * Acorda Therapeutics, Inc., Hawthorne, New York, USA AR Blight Authors * JA Halter View author publications You can also search for this

author inPubMed Google Scholar * AR Blight View author publications You can also search for this author inPubMed Google Scholar * WH Donovan View author publications You can also search for

this author inPubMed Google Scholar * O Calvillo View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT

THIS ARTICLE CITE THIS ARTICLE Halter, J., Blight, A., Donovan, W. _et al._ Intrathecal administration of 4-aminopyridine in chronic spinal injured patients. _Spinal Cord_ 38, 728–732

(2000). https://doi.org/10.1038/sj.sc.3101098 Download citation * Published: 12 January 2001 * Issue Date: 01 December 2000 * DOI: https://doi.org/10.1038/sj.sc.3101098 SHARE THIS ARTICLE

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by the Springer Nature SharedIt content-sharing initiative KEYWORDS * spinal cord injury * intrathecal * 4-aminopyridine * neural plasticity * axon