Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: a long-term, controlled trial.
OBJECTIVE
To determine the effects of the long-term administration of 4-aminopyridine (4-AP) on sensorimotor function in humans with long-standing spinal cord injury (SCI).


METHODS
Randomized, open-label, active-treatment control, dosage-blinded study.


METHODS
University-affiliated, tertiary-level care, Department of Veterans Affairs Medical Center.


METHODS
Twenty-one healthy men and women outpatients suffering from traumatic SCI (14 tetraplegic, 7 paraplegic) for 2 years or more.


METHODS
Dosages of an immediate-release formulation of 4-AP were titrated. At 3 months, 16 subjects were receiving 4-AP 30 mg/day (high dose); 5 subjects were receiving 4-AP 6 mg/day (low dose) and served as an active-treatment control group.


RESULTS
Composite motor and sensory scores had statistically significant increases at 3 months. Maximal expiratory pressure, maximal inspiratory pressure, forced vital capacity, and forced expiratory volume in 1 second showed clinically meaningful and/or statistically significant increases among patients receiving 4-AP 30 mg/day. These subjects also had significant decreases in spasticity (modified Ashworth Scale). Serial biochemical profiles and electroencephalographs were unchanged from baseline, and no clinically significant drug toxicity was encountered.


CONCLUSIONS
Long-term oral administration of immediate-release 4-AP was associated with improvement in and recovery of sensory and motor function, enhanced pulmonary function, and diminished spasticity in patients with long-standing SCI. 4-Aminopyridine appears to be safe and relatively free from toxicity when administered orally over 3 months. Each patient who received immediate-release 4-AP 30 mg/day showed a response in one or more of the outcome measures.
Segal
J L
JL
Department of Medicine, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Pathak
M S
MS
Hernandez
J P
JP
Himber
P L
PL
Brunnemann
S R
SR
Charter
R S
RS
D015761:4-Aminopyridine / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002490:Central Nervous System / Q000187:drug effects*; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D026902:Potassium Channel Blockers; D011597:Psychomotor Performance / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
D026902:Potassium Channel Blockers; D015761:4-Aminopyridine