title: Comparison of 10-mg doses of 4-aminopyridine and 3,4-diaminopyridine for the treatment of downbeat nystagmus.
abstract: OBJECTIVE
  Animal experiments have demonstrated that aminopyridines increase Purkinje cell excitability, and in clinical studies, 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) improved downbeat nystagmus. In this double-blind, prospective, crossover study, the effects of equivalent doses of 4-AP and 3,4-DAP on the slow-phase velocity (SPV) of downbeat nystagmus were compared.
  
  
  METHODS
  Eight patients with downbeat nystagmus due to different etiologies (cerebellar degeneration [n = 1], bilateral vestibulopathy [n = 1], bilateral vestibulopathy and cerebellar degeneration [n = 1], Arnold-Chiari I malformation and cerebellar ataxia [n = 1], cryptogenic cerebellar ataxia [n = 4]) were included. They were randomly assigned to receiving a single capsule of 10 mg of 3,4-DAP or 4-AP followed by 6 days with no medication. One week later, the treatment was switched, that is, 1 single capsule (10 mg) of the other agent. Recordings with 3-dimensional video-oculography were performed before and 45 and 90 minutes after drug administration.
  
  
  RESULTS
  Both medications had a significant effect throughout time (pre vs post 45 vs post 90) (F() = 8.876; P < 0.01). Following the 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) (pre vs post 45/post 90 P < 0.01). In 4-AP, the mean SPV decreased from -6.04°/s (pre) to -1.58°/s (post 45) to -1.21°/s (post 90) (pre vs post 45/post 90 P < 0.00001). Both after 45 and after 90, the mean SPVs were significantly lower for 4-AP than for 3,4-DAP (P < 0.05). None of the patients reported serious side effects.
  
  
  CONCLUSIONS
  Based on these results, 10-mg doses of 4-AP lead to a more pronounced decrease of the SPV of downbeat nystagmus than do equivalent doses of 3,4-DAP.
authors: Department of Neurology and IFB, Munich University Hospital, Campus Grosshadern, Munich, Germany.
authors: Roger
authors: R
authors: Kalla
authors: Rainer
authors: R
authors: Spiegel
authors: Jens
authors: J
authors: Claassen
authors: Stanislavs
authors: S
authors: Bardins
authors: Ales
authors: A
authors: Hahn
authors: Erich
authors: E
authors: Schneider
authors: Nicole
authors: N
authors: Rettinger
authors: Stefan
authors: S
authors: Glasauer
authors: Thomas
authors: T
authors: Brandt
authors: Michael
authors: M
authors: Strupp
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000077770:Amifampridine; D002214:Capsules; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005133:Eye Movements / Q000502:physiology; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D009759:Nystagmus, Pathologic / Q000188:drug therapy* / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D014741:Video Recording
chemical_list: D002214:Capsules; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; D000077770:Amifampridine