Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: a long-term, controlled trial.

Abstract

STUDY 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).

DESIGN:

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

SETTING:

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

PATIENTS:

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

INTERVENTIONS:

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.

MEASUREMENTS AND MAIN 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: J L Segal, M S Pathak, J P Hernandez, P L Himber, S R Brunnemann, R S Charter
• Journal: Pharmacotherapy (Pharmacotherapy) Vol. 19 Issue 6 Pg. 713-23 (Jun 1999) ISSN: 0277-0008 [Print] United States
• PMID: 10391417 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channel Blockers
• 4-Aminopyridine

Topics

• 4-Aminopyridine (administration & dosage, pharmacology)
• Administration, Oral
• Adult
• Aged
• Central Nervous System (drug effects)
• Cohort Studies
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Potassium Channel Blockers
• Psychomotor Performance (drug effects)
• Spinal Cord Injuries (drug therapy, physiopathology)
• Time Factors
• Treatment Outcome