Preclinical trial of 4-aminopyridine in patients with chronic spinal cord injury.
4-Aminopyridine (4-AP) is a K+ channel blocking agent that enhances nerve conduction through areas of demyelination by prolonging the duration of the action potential and increasing the safety factor for conduction. We have investigated the effects of 4-AP (24 mg total dose-intravenous) in 6 patients with spinal cord injury (3 complete, 3 incomplete) with the intent of overcoming central conduction block, or slowing, due to demyelination. Vital signs remained stable and only mild side effects were noted. The 3 patients with incomplete injuries all demonstrated enhanced volitional EMG interference patterns and one patient exhibited restored toe movements. The changes were reversed on drug washout. There were no changes in segmental reflex activities. These results are consistent with those obtained from 4-AP trials with animal models of spinal cord injury, showing modest therapeutic benefit attributable to enhanced central conduction.
Department of Physical Medicine & Rehabilitation, Parkwood Hospital, London, Ontario, Canada.
K C
KC
Hayes
A R
AR
Blight
P J
PJ
Potter
R D
RD
Allatt
J T
JT
Hsieh
D L
DL
Wolfe
S
S
Lam
J T
JT
Hamilton
D015761:4-Aminopyridine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000652:urine; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002908:Chronic Disease; D004341:Drug Evaluation; D004569:Electroencephalography; D004576:Electromyography; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009068:Movement / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology
D015761:4-Aminopyridine