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November 1994

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

Author Affiliations

From the Departments of Neurology (Drs Polman, Bertelsmann, de Waal, van Diemen, Uitdehaag, and Koetsier) and Pharmacy (Mr van Loenen), Free University Hospital, Amsterdam, the Netherlands.

Arch Neurol. 1994;51(11):1136-1139. doi:10.1001/archneur.1994.00540230074016

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.

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