title: Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: a long-term, controlled trial.
abstract: 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.
authors.affiliation: Department of Medicine, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Segal
authors.forename: M S
authors.initials: MS
authors.lastname: Pathak
authors.forename: J P
authors.initials: JP
authors.lastname: Hernandez
authors.forename: P L
authors.initials: PL
authors.lastname: Himber
authors.forename: S R
authors.initials: SR
authors.lastname: Brunnemann
authors.forename: R S
authors.initials: RS
authors.lastname: Charter
mesh_terms: 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
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine