The effects of 4-aminopyridine on focal nerve conduction block

In order to test whether 4-aminopyridine (4-AP), a potassium channel blocker, may be of therapeutic value in demyelinating neuropathies, a focal tibial nerve conduction block with demyelination was produced in adult rats by an intraneural microinjection of potassium tellurite. Onset and recovery of the lesion were monitored by evoked compound muscle action potentials (CMAP) activated from the proximal and distal nerve one day before and 1, 4, 7, 14, 21 and 28 days after the injection. Intraperitoneal 4-AP (2 mg/kg) or buffered saline were injected prior to the potassium tellurite and 6 days per week for 28 days. The data show that 4-AP is tolerated, it does not prevent conduction block, and only has a modest effect on increasing its recovery from day 4 to 7 (91 % increase in CMAP ratio compared with control of 35%). Recovery is similar by day 28 in 4-AP treated or untreated animals. These results suggest that 4-AP will have limited use in the therapy of subacute demyelinating neuropathies.