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4-Aminopyridine in multiple sclerosis

Prolonged administration

Rush Multiple Sclerosis Center and the Departments of Neurological Sciences (Drs. Stefoski and Davis, and J. Rush), Pharmacy (Drs. Fitzsimmons and Luskin), and Pharmacology (Dr. Parkhurst), Rush University, Chicago, IL.

In an earlier study, we demonstrated efficacy of single oral doses of 4-aminopyridine (4-AP) in improving motor and visual signs in multiple sclerosis (MS) patients for a mean of 4.97 hours. We attempted to determine whether efficacy could safely be prolonged using multiple daily doses over several days by administering 7.5 to 52.5 mg 4-AP to 17 temperature-sensitive MS patients in one to three daily doses at 3- to 4-hour intervals over 1 to 5 days in a double-blind study. Nine of these patients were also tested with identically appearing placebo. Thirteen of the 17 patients (76%) given 4-AP showed clinically important motor and visual improvements compared with three of nine in the placebo group. Average peak improvement scores were 0.40 for 4-AP and 0.12 for placebo. Seventy percent of the daily 4-AP improvements lasted 7 to 10 hours. The improvements for two consecutive doses of 4-AP lasted a mean of 7.07 hours (83% of the average 8.53-hour treatment-observation period) compared with 2.36 hours for placebo (26% of the average 9.06-hour treatment-observation period). No serious side effects occurred. 4-AP is a promising drug for the symptomatic treatment of MS.

Address correspondence and reprint requests to Dr. D. Stefoski, Rush Multiple Sclerosis Center, 1725 West Harrison #330, Chicago, IL 60612.

Supported by the John Ruan MS Charity.

Presented in part at the 42nd annual meeting of the American Academy of Neurology, Miami Beach, FL, May 1990.

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