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The Effects of 4-Aminopyridine in MS Pts:Randomized, Placebo-Controlled, Double-Blind, Concentration-Controlled, Crossover Neurol 44:1054-1059, Bever,C.T.,et al, 1994 See this aricle in Pubmed Article Abstract Because 4-aminopyridine(AP)improves residual deficits in some multiple sclerosis(MS)patients but has a narrow toxic-to-therapeutic margin,we compared the safety and efficacy of two target peak serum concentration ranges(low:30 to 59 ng/ml and high:60 to 100 ng/ml).All patients experienced side effects during the high-serum-concentration arm.A grand mal seizure occurred at a serum AP level of 104 ng/ml,and an acute confusional episode occurred at 114 ng/ml.AP treatment produced improvements in residual deficits in MS patients,but the occurrence of significant toxicity suggests that AP serum levels should be monitored and peak levels above 100 ng/ml should be avoided.Concentration-control methodology may be useful in testing putative treatments for other neurologic disease.

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