A double-blind placebo-controlled study of 3,4-diaminopyridine in amytrophic lateral sclerosis patients on a rehabilitation unit.

3,4-Diaminopyridine (DAP) enhances acetylcholine release from the nerve terminal and improves conduction in demyelinated axons. In this double-blinded placebo controlled cross over study we examined the effects of DAP combined with inpatient rehabilitation in nine patients with disabling motor weakness due to amyotrophic lateral sclerosis (ALS). A single dose of DAP or placebo was increased daily to the maximum (range: 10-80 mg) tolerated dose; after patients were assessed on the first treatment, the alternate drug was given in the same manner. Functional Independence Measurement (FIM), Ashworth, grip strength, limb strength measurements, nerve conduction studies and speech assessments were initiated 1/2 h after receiving the maximum tolerated dose of DAP or placebo. DAP was tolerated in all patients, but limited by gastrointestinal side effects in four patients. The mean peak serum level was 20.11 (S.D. = 5.11) ng/ml, occurring 1.25 (S.D. = 0.56) h after dose. A statistically significant improvement in FIM and speech assessment scores between admission and discharge occurred. However, no significant differences in clinical or electrophysiologic measures were seen between DAP and placebo treatments. This study suggests that intensive inpatient rehabilitation has a role in the management of patients with ALS, but DAP does not diminish motor impairment.