4-Aminopyridine Is Superior to 3,4-Diaminopyridine in the Treatment of Patients With Multiple Sclerosis

Objective: To compare the efficacy and toxicity of 4-aminopyridine and 3,4-diaminopyridine in patients with multiple sclerosis. Design: Intervention study with a before-after design and a randomized, double-blind, crossover design. Setting: University referral center. Patients: Twenty-four patients with definite multiple sclerosis who had been treated in a previous clinical trial with 4-aminopyridine. Interventions: Nonresponders to treatment with 4-aminopyridine (14 patients) were treated with 3,4-diaminopyridine in a 4-week, open-label trial with doses up to 1.0 mg/kg of body weight (before-after design). Responders to treatment with 4-aminopyridine (10 patients) participated in a comparative study of 6 weeks' duration with 4-aminopyridine and 3,4-diaminopyridine according to a randomized, double-blind, double-crossover design. Main Outcome Measures: Neurophysiologic variables for nonresponders, neurologic functions and symptoms on a visual analogue scale for responders, and side effects for both groups. Results: Toxicity profiles of 4-aminopyridine and 3,4-diaminopyridine were different, and systemic tolerability was reduced for 3,4-diaminopyridine. 4-Aminopyridine was more effective than 3,4-diaminopyridine, especially for ambulation, fatigue, and overall daily functioning. Conclusion: Our data suggest that, concerning both efficacy and side effects, 4-aminopyridine is superior to 3,4-diaminopyridine in the treatment of patients with multiple sclerosis.