Physiological effects of 4‐aminopyridine on demyelinated mammalian motor and sensory fibers

Abstract

The selective response of demyelinated sensory fibers to 4‐aminopyridine (4‐AP) has been proposed as a mechanism underlying the reported paresthesias that complicate the use of this potassium‐channel blocking agent in clinical trials for the treatment of multiple sclerosis and neuromuscular disorders. To identify differences in the electrophysiological response of specific fiber types to the application of 4‐AP, rat ventral and dorsal spinal roots, demyelinated by intrathecal injections of lysophosphatidylcholine, were examined in vitro before and during potassium‐channel blockade. The compound action potentials of demyelinated ventral roots showed a prominent postspike negativity associated with a broadening of single action potentials following application of 4‐AP. Under similar conditions, whole root responses of demyelinated dorsal root axons also developed a late negativity, but individual fibers were observed to fire repetitively in response to a single stimulus. The data support the hypothesis that the prominent sensory dysfunctions reported in clinical trials of 4‐AP are due to the selective response characteristics of sensory fibers. Copyright © 1987 American Neurological Association