4-Aminopyridine may be more effective than 3,4-Diaminopyridine for downbeat nystagmus

This small, double-blind, crossover study published in December 2011 in the Journal of Neuro-Ophthalmology compared the effects of single doses (10 mg) of 4-aminopyridine (4-AP) or 3,4-diaminopyridine (3,4-DAP) on the mean slow-phase velocity (SPV) in patients with downbeat nystagmus (DBN). While both 4-AP and 3,4-DAP have previously been shown to decrease the mean SPV of DBN, the study’s results found that 4-AP decreased the intensity of DBN significantly more than 3,4-DAP.

Subjects were eight patients with downbeat nystagmus of different etiologiesrandomly assigned a single capsule of 10 mg of 3,4-DAP or 4-AP followed by six days with no medication. One week later, the treatment was switched, and they received a single capsule (10 mg) of the other agent. Recordings with 3-dimensional video-oculography were performed before patients took the medication and 45 and 90 minutes after drug administration.

Both medications had a significant effect. Following administration of 3,4-DAP, mean slow velocity decreased from 5.68°/s (pre) to 3.29°/s (post 45) to 2.96°/s (post 90). With 4-AP, the mean SPV decreased from 6.04°/s (pre) to 1.58°/s (post 45) to 1.21°/s (post 90). After both 45 and 90 minutes, the mean SPVs were significantly lower for 4-AP than for 3,4-DAP (P < 0.05). No serious side effects were reported.

The authors conclude that the differences between the effects of 4-AP and 3,4-DAP may be due to different pharmacokinetics and the action of the two aminopyridines in blocking cellular potassium channels. Given that DBN is a central ocular motor disorder, they say that 4-AP would be expected to have a greater effect on DBN. They say that future studies should consider other parameters, including visual acuity, nystagmus amplitude and nystagmus frequency.