The use of aminopyridines in neurological disorders

Clinical Neuropharmacology

Volumn 35, Issue 4, 2012, Pages 191-200

  Sedehizadeh, Saam ^a   Keogh, Michael ^b   Maddison, Paul ^a  

^a QUEEN S MEDICAL CENTRE   (United Kingdom)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

3,4 diaminopyridine; 4 aminopyridine; Alzheimer disease; cerebellar ataxia; congenital myasthenia; demyelinating neuropathy; essential tremor; Lambert Eaton myasthenic syndrome; meta analysis; motor neurone disease; multiple sclerosis; nystagmus; spinal cord injury

Indexed keywords

3,4 DIAMINOPYRIDINE; 4 AMINOPYRIDINE; AMINOPYRIDINE; BACLOFEN; CHOLINESTERASE INHIBITOR; CLONAZEPAM; GABAPENTIN; MEMANTINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; PLACEBO; TIZANIDINE; TRIHEXYPHENIDYL;

ABDOMINAL PAIN; ACUTE BRAIN DISEASE; AGITATION; ALZHEIMER DISEASE; ANXIETY DISORDER; BLOOD BRAIN BARRIER; BLURRED VISION; BRAIN ELECTROPHYSIOLOGY; CEREBELLUM DISEASE; CHROMOSOME 19P; COMPARATIVE STUDY; CONGENITAL MYASTHENIC SYNDROME; DELIRIUM; DEMYELINATING NEUROPATHY; DIARRHEA; DISTAL PARESTHESIA; DIZZINESS; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; EATON LAMBERT SYNDROME; ELECTROCARDIOGRAM; ESSENTIAL TREMOR; FOLLOW UP; FOOD AND DRUG ADMINISTRATION; GAIT DISORDER; GUILLAIN BARRE SYNDROME; HEART PALPITATION; HEPATITIS; HUMAN; INSOMNIA; META ANALYSIS; MOTOR NEURON DISEASE; MULTIPLE SCLEROSIS; NEUROLOGIC DISEASE; NEUROTOXICITY; NYSTAGMUS; ORAL PARESTHESIA; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCORING SYSTEM; SEIZURE; SIDE EFFECT; SLOW DRUG RELEASE; SPASTICITY; SPINAL CORD INJURY; SUPRAVENTRICULAR TACHYCARDIA; SYSTEMATIC REVIEW; TREATMENT DURATION;

4-AMINOPYRIDINE; AMINOPYRIDINES; ANIMALS; HUMANS; LAMBERT-EATON MYASTHENIC SYNDROME; NERVOUS SYSTEM DISEASES; POTASSIUM CHANNEL BLOCKERS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84863931364     PISSN: 03625664     EISSN: 1537162X     Source Type: Journal    
DOI: 10.1097/WNF.0b013e31825a68c5     Document Type: Review

References (113)

1. Yeh JZ, Oxford GS, Wu CH, et al. Dynamics of aminopyridine block of potassium channels in squid axon membrane. J Gen Physiol 1976;68:519-535.
2. Bostock H, Sherratt RM, Sears TA. Overcoming conduction failure in demyelinated nerve fibres by prolonging action potentials. Nature 1978;274:385-387. (Pubitemid 8387340)
3. Kim YI, Goldner MM, Sanders DB. Facilitatory effects of 4-aminopyridine on neuromuscular transmission in disease states. Muscle Nerve 1980;3:112-119. (Pubitemid 10134617)
4. Smith KJ, Felts PA, John GR. Effects of 4-aminopyridine on demyelinated axons, synapses and muscle tension. Brain 2000;123(Pt 1):171-184. (Pubitemid 30037979)
5. Waxman SG. Pathophysiology of demyelinated and remyelinated axons. In: Cook SD, ed. Handbook of multiple sclerosis. 2nd ed. New York, NY: Marcel Dekker; 1996:257-294.
6. Sherrat RM, Bostock H, Sears TA. Effects of 4-aminopyridine on normal and demyelinated mammalian nerve fibers. Nature 1980;283:570-572. (Pubitemid 10136031)
7. Kim YI, Goldner MM, Sanders DB. Facilitatory effects of 4-aminopyridine on normal neuromuscular transmission. Muscle Nerve 1980;3:105-111. (Pubitemid 10134616)
8. Agoston S, Maestrone E, van Hezik EJ, et al. Effective treatment of verapamil intoxication with 4-aminopyridine in the cat. J Clin Invest 1984;73:1291-1296. (Pubitemid 14139523)
9. Agoston S, van Weerden T, Westra P, et al. Effects of 4-aminopyridine in Eaton Lambert Syndrome. Br J Anaesth 1978;50:383-385. (Pubitemid 9055537)
10. Davis LE, Johnson JK, Bicknell JM, et al. Human type A botulism and treatment with 3, 4-diaminopyridine. Electromyogr Clin Neurophysiol 1992;32(7-8):379-383.
11. Palace J, Wiles CM, Newsom-Davis J. 3, 4-diaminopyridine in the treatment of congenital (hereditary) myasthenia. J Neurol Neurosurg Psychiatry 1991;54:1069-1072.
12. Davis FA, Stefoski D, Rush J. Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis. Ann Neurol 1990;27:186-192. (Pubitemid 20086640)
13. Meythaler JM, Guin-Renfroe S, Johnson A, et al. The safety and efficacy of 4-aminopyridine for motor weakness due to Guillain-Barré syndrome: a double-blind cross-over phase I drug trial. Arch Phys Med Rehabil 2000;81:1293.
14. Wesseling H, Agoston S, Van Dam GB, et al. Effects of 4-aminopyridine in elderly patients with Alzheimer's disease. N Engl J Med 1984;310:988-989. (Pubitemid 14173243)
15. Sprenger A, Rambold H, Sander T, et al. Treatment of the gravity dependence of downbeat nystagmus with 3, 4-diaminopyridine. Neurology 2006;67(5):905-907. (Pubitemid 44394219)
16. Lorenz D, Hagen K, Ufer M, et al. No benefit of 3, 4-diaminopyridine in essential tremor: a placebo-controlled study. Neurology 2006;66(11):1753-1755. (Pubitemid 43964639)
17. Doc M, Ali AB, Karras A, et al. Treatment of severe botulism with 3, 4-diaminopyridine, Presse Med 2002;31:601-602.
18. Lundh H, Fehling C. Lack of effect of 4-aminopyridine on choreic movements. J Neurol Neurosurg Psychiatry 1982;45(3):274-276.
19. Wesseling H, Lakke JPWF. Observations with 4-aminopyridine in Huntington's chorea. IRCS Med Sci 1980;8:332-333. (Pubitemid 10031736)
20. McEvoy KM, Windebank AJ, Daube JR, et al. 3, 4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome. N Engl J Med 1989;321:1567-1571. (Pubitemid 20008235)
21. Sanders DB, Massey JM, Sanders LL, et al. A randomized trial of 3, 4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 2000;54:603-607. (Pubitemid 30082925)
22. Wirtz PW, Verschuuren JJ, van Dijk JG, et al. Efficacy of 3, 4-diaminopyridine and pyridostigmine in the treatment of Lambert-Eaton myasthenic syndrome: a randomized, double-blind, placebo-controlled, cross-over study. Clin Pharmacol Ther 2009;86:44-48.
23. Oh SJ, Claussen GG, Hatanaka Y, et al. 3, 4-diaminopyridine is more effective than placebo in a randomized, double-blind, cross-over drug study in LEMS. Muscle Nerve 2009;40:795-800.
24. Bever CT Jr, Young D, Tierney D, et al. The pharmacokinetics and tolerability of a slow-release formulation of 4-aminopyridine in multiple sclerosis patients. Neurology 1995;45(suppl 4):A351.
25. Rossini PM, Pasqualetti P, Pozzilli C, et al. Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine. Mult Scler 2001;7:354-358. (Pubitemid 33138344)
26. Smits RC, Emmen HH, Bertelsmann FW, et al. The effects of 4-aminopyridine on cognitive function in patients with multiple sclerosis: a pilot study. Neurology 1994;44:1701-1705. (Pubitemid 24286651)
27. van Diemen HA, Polman CH, van Dongen TM, et al. The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study. Ann Neurol 1992;32:123-130.
28. Schwid SR, Petrie MD, McDermott MP, et al. Quantitative assessment of sustained release 4-aminopyridine for symptomatic treatment of multiple sclerosis. Neurology 1997;48:817-821.
29. Goodman AD, Blight A, Cohen JA, et al. Placebo-controlled double-blinded dose ranging study of fampridine-SR in multiple sclerosis. Neurology 2003;60:A167.
30. Goodman AD, Brown TR, Cohen JA, et al. Fampridine MS-F202 Study Group. Dose comparison trial of sustained-release fampridine in multiple sclerosis. Neurology 2008;71:1134-1141.
31. Goodman A, Brown TR, Krupp LB, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double blind, controlled trial. Lancet 2009;373:732-738.
32. Goodman A, Brown TR, Edwards KR, et al. A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Ann Neurol 2010;68:494-502.
33. Hansebout RR, Blight AR, Fawcett S, et al. 4-Aminopyridine in chronic spinal cord injury: a controlled, double-blind, crossover study in eight patients. J Neurotrauma 1993;10:1-18. (Pubitemid 23153141)
34. Segal JL, Pathak MS, Hernandez JP, et al. Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: a long-term, controlled trial. Pharmacotherapy 1999;19:713-723. (Pubitemid 29277971)
35. Wolfe DL, Hayes KC, Hsieh JT, et al. Effects of 4-aminopyridine on motor evoked potentials in patients with spinal cord injury: a double-blinded, placebo-controlled crossover trial. J Neurotrauma 2001;18:757-771. (Pubitemid 32769772)
36. van der Bruggen MA, Huisman HB, Beckerman H, et al. Randomized trial of 4-aminopyridine in patients with chronic incomplete spinal cord injury. J Neurol 2001;248:665-671. (Pubitemid 32695862)
37. Grijalva I, Guizar-Sahagun G, Castaneda-Hernandez G, et al. Efficacy and safety of 4-aminopyridine in patients with long-term spinal cord injury: a randomized, double-blind, placebo-controlled trial. Pharmacotherapy 2003;23:823-834. (Pubitemid 36875665)
38. Wakana CI, Segal JL. Effects of 4-aminopyridine on cardiac repolarization, PR interval, and heart rate in patients with spinal cord injury. Pharmacotherapy 2003;23:133-136. (Pubitemid 36204017)
39. Potter PJ, Hayes KC, Segal JL, et al. Randomized double-blind crossover trial of fampridine-SR (sustained-release 4-aminopyridine) in patients with incomplete spinal cord injury. J Neurotrauma 1998;10:837-849. (Pubitemid 28487997)
40. Ditunno JF Jr, Graziani V, Katz MA, et al. Double-blind, placebo-controlled, dose-escalating study evaluating the safety and efficacy of oral doses of fampridine-SR (sustained-release 4-aminopyridine) in patients with chronic spinal cord injury. J Spinal Cord Med 2002;25:S1-S38.
41. Lammertse D, Graziani V, Katz MA. Safety and efficacy of oral fampridine-SR (sustained-release 4-aminopyridine) in patients with chronic motor-incomplete spinal cord injury. J Spinal Cord Med 2002;25:S5.
42. Cardenas D, Ditunno J, Graziani V, et al. Phase 2 trial of sustained-release fampridine in chronic spinal cord injury. Spinal Cord 2007;45(2):158-168. (Pubitemid 46204264)
43. Strupp M, Kalla R, Claassen J, et al. A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias. Neurology 2011;77:269-275.
44. Strupp M, Schuler O, Krafczyk S, et al. Treatment of downbeat nystagmus with 3, 4-diaminopyridine A placebo-controlled study. Neurology 2003;61:165-170. (Pubitemid 36875295)
45. Kalla R, Spiegel R, Claassen J, et al. Comparison of 10-mg doses of 4-aminopyridine and 3, 4-diaminopyridine for the treatment of downbeat nystagmus. J Neuroophthalmol 2011;31(4):320-325.
46. Kalla R, Glasauer S, Büttner U, et al. 4-Aminopyridine restores vertical and horizontal neural integrator function in downbeat nystagmus. Brain 2007;130:2441-2451. (Pubitemid 47327634)
47. Russell JW, Windebank AJ, Harper CM Jr. Treatment of stable chronic demyelinating polyneuropathy with 3, 4-Diaminopyridine. Mayo Clin Proc 1995;70:532-539.
48. Davidson M, Zemishlany Z, Mohs RC, et al. 4-aminopyrdine in the treatment of Alzheimer's disease. Biol Psychiatry 1988;23(5):485-490.
49. Anlar B, Varli K, Ozdirim E, et al. 3, 4-Diaminopyridine in childhood myasthenia: double blind, placebo controlled trial. J Child Neurol 1996;11:458-461.
50. Aisen ML, Sevilla D, Edelstein L, et al. A double-blind placebo-controlled study of 3, 4-diaminopyridine in amytrophic lateral sclerosis patients on a rehabilitation unit. J Neurol Sci 1996;138:93-96. (Pubitemid 26195860)
51. Murray NMF, Newsom-Davis J. Treatment with oral 4-aminopyridine in disorders of neuromuscular transmission. Neurology 1981;31:265-271. (Pubitemid 11146987)
52. Stefoski D, Davis FA, Faut M, et al. 4-Aminopyridine improves clinical signs in multiple sclerosis. Ann Neurol 1987;21:71-77. (Pubitemid 17004147)
53. Lundh H, Nilsson O, Rosén I, et al. a new drug tested in the treatment of Eaton-Lambert syndrome. J Neurol Neurosurg Psychiatry 1977;40:1109-1112. (Pubitemid 8261762)
54. Hayes KC, Potter PJ, Wolfe DL, et al. 4-aminopyridine-sensitive neurologic deficits in patients with spinal cord injury. J Neurotrauma 1994;11:433-446. (Pubitemid 24304694)
55. Bergin PS, Miller DH, Hirsch NP, et al. Failure of 3, 4-diaminopyrdine to reverse conduction block in inflammatory demyelinating neuropathies. Ann Neurol 1993;34(3):406-409. (Pubitemid 23259613)
56. Aisen ML, Sevilla D, Gibson G, et al. 3, 4-Diaminpyridine as a treatment for amyotrophic lateral sclerosis. J Neurol Sci 1995;129:21-24.
57. Sprenger A, Zilis E, Rambold H, et al. Effect of 3, 4-Diaminopyridine on the postural control in patients with downbeat nystagmus. Ann N Y Acad Sci 2005;1039:395-403. (Pubitemid 40979897)
58. Schniepp R, Wuehr M, Ackl N, et al. 4-Aminopyridine improves gait variability in cerebellar ataxia due to CACNA 1A mutation. J Neurol 2011;258:1708-1711.
59. Tsunemi T, Ishikawa K, Tsukui K, et al. The effect of 3, 4-diaminopyridine on the patients with hereditary pure cerebellar ataxia. J Neurol Sci 2010;292:81-84.
60. Strupp M, Kalla R, Dichgans M, et al. Treatment of episodic ataxia type 2 with the potassium channel blocker 4 aminopyridine. Neurology 2004;62:1623-1625. (Pubitemid 38608211)
61. Glasauer S, Kalla R, Büttner U, et al. 4-aminopyridine restores visual ocular motor function in upbeat nystagmus. J Neurol Neurosurg Psychiatry 2005;76:451-453. (Pubitemid 40299147)
62. Sanders DB, Massey JM, Howard JF Jr. 3, 4-Diamimopyridine in myasthenia gravis and Lambert-Eaton syndrome. Neurology 1989;39:267A.
63. Lambert EH, Eaton LM, Rooke ED. Defect of neuromuscular conduction associated with malignant neoplasms. Am J Physiol 1956;187:612-613.
64. Lambert EH, Elmqvist D. Quantal components of end-plate potentials in the myasthenic syndrome. Ann NY Acad Sci 1971;183:183-199.
65. O'Neill JH, Murray NMF, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome: a review of 50 cases. Brain 1988;111:577-596.
66. Wirtz PW, van Dijk JG, van Doorn PA, et al. The epidemiology of the Lambert-Eaton myasthenic syndrome in the Netherlands. Neurology 2004;63:397-398. (Pubitemid 38971159)
67. Lang B, Newsom-Davis J, Wray D, et al. Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet 1981;2(8240):224-226. (Pubitemid 11095446)
68. Lennon VA, Kryzer TJ, Griesmann GE, et al. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 1995;332:1467-1474.
69. Motomura M, Johnston I, Lang B, et al. An improved diagnostic assay for Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 1995;58:85-87.
70. Lundh H. Effects of 4-aminopyridine on neuromuscular transmission. Brain Res 1978;153:307-318. (Pubitemid 8387960)
71. BioMarin Europe Ltd. Summary of Product Characteristics. Firdapse\ (amifampridine). Date of Preparation of Text January 2010.
72. Deeks JJ, Higgins JPT, Altman DG. Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2. Chichester, UK: John Wiley & Sons; 2009.
73. Keogh MJ, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome 2010. Cochrane Database Syst Rev 2011;(2):CD003279.
74. Boerma CE, Rommes JH, van Leeuwen RB, et al. Cardiac arrest following an iatrogenic 3, 4-diaminopyridine intoxication in a patient with Lambert-Eaton myasthenic syndrome. J Toxicol Clin Toxicol 1995;33:249-251.
75. Hawkes N, Cohen D. What makes an orphan drug? BMJ 2010;341:1076-1078.
76. Ferner RE, Hughes DA. The problem of orphan drugs. BMJ 2010;341:1059-1060.
77. Barohn RJ, McIntire D, Herbelin L, et al. Reliability testing of the quantitative myasthenia gravis score. Ann NY Acad Sci 1998;841:769-772. (Pubitemid 28362935)
78. Maddison P, McConville J, Farrugia ME, et al. The use of rituximab in myasthenia gravis and Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 2010;82(6):671-673.
79. Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. Annu Rev Immunol 1992;10:153-187.
80. Waxman SG. Membranes, myelin, and the pathophysiology of multiple sclerosis. N Engl J Med 1982;306:1529-1533. (Pubitemid 12123934)
81. Solari A, Uitdehaag B, Giuliani G, et al. Aminopyridines for symptomatic treatment in multiple sclerosis. Cochrane Database Syst Rev 2003;CD001330 (updated 2009, Issue 1).
82. European Medicines Agency. Refusal of the marketing authorisation for Fampyra (fampridine). Available at: http://www.ema.europa.eu/docs/en-GB/ document-library/Summary-of-opinion-Initial-authorisation/human/002097/ WC500101071.pdf. Accessed November 1, 2011.
83. European Medicines Agency. Positive Opinion on the marketing authorisation for Fampyra (fampridine). http://www.ema.europa.eu/docs/en-GB/ document-library/Medicine-QA/human/002097/WC500106540.pdf. Accessed November 1, 2011.
84. Summary of Product Characteristics for Fampridine. Available at: http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/ human/002097/WC500109956.pdf. Accessed November 1, 2011.
85. Hayes K. The use of 4-aminopyridine (fampridine) in demyelinating disorders. CNS Drug Rev 2004;10(4):295-316. (Pubitemid 40128914)
86. Hugon J, Lubeau M, Tabaraud F, et al. Central motor conduction in motor neuron disease. Ann Neurol 1987;22:544-546. (Pubitemid 17164781)
87. Bertorini T, Rashed H, Zeno M, et al. Effects of 3-4 diaminopyridine (DAP) in motor neuron diseases. J Clin Neuromusc Dis 2011;12:129-137.
88. Robinson DA, Zee DS, Hain TC, et al. Alexander's law: its behavior and origin in the human vestibulo-ocular reflex. Ann Neurol 1984;16:714-722. (Pubitemid 15177676)
89. Leigh RJ, Zee DS. The Neurology of Eye Movements. 3rd ed. Philadelphia, PA: Davis; 1999.
90. Etzion Y, Grossman Y. Highly 4-aminopyridine sensitive delayed rectifier current modulates the excitability of guinea pig cerebellar Purkinje cells. Exp Brain Res 2001;139:419-425. (Pubitemid 32703948)
91. Alvina K, Khodakhah K. The therapeutic mode of action of 4-aminopyridine in cerebellar ataxia. J Neurosci 2010;30:7258-7268.
92. Judge SI, Bever CT Jr. Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment. Pharmacol Ther 2006;111:224-259. (Pubitemid 43765538)
93. Hayes KC, Katz MA, Devane JG, et al. Pharmacokinetics of an immediate-release oral formulation of fampridine (4-aminopyridine) in normal subjects and patients with spinal cord injury. J Clin Pharmacol 2003;43:379-385. (Pubitemid 36368779)
94. Lemeignan M, Millart H, Letteron N, et al. The ability of 4-aminopyridine and 3, 4-diaminopyridine to cross the blood-brain barrier can account for their difference in toxicity. In: Lechat P, Thesleff S, Bowman WC, eds. Aminopyridines and Similarly Acting Drugs: Effects on Nerves, Muscles and Synapses. Advances in the Biosciences. Vol. 35. Oxford, UK: Pergamon Press; 1982:222-229. (Pubitemid 13033832)
95. Jen J, Kim GW, Baloh RW. Clinical spectrum of episodic ataxia type 2. Neurology 2004;62:17-22. (Pubitemid 38082863)
96. Jodice C, Mantuano E, Veneziano L, et al. Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p. Hum Mol Genet 1997;6:1973-1978. (Pubitemid 27460375)
97. Kullmann DM. The neuronal channelopathies. Brain 2002;125:1177-1195. (Pubitemid 34587130)
98. Griggs RC, Nutt JG. Episodic ataxias as channelopathies. Ann Neurol 1995;37:285-287.
99. Jen JC, Graves TD, Hess EJ, et al. Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain 2007;130:2484-2493. (Pubitemid 47511698)
100. Deuschl G, Elble RJ. The pathophysiology of essential tremor. Neurology 2000;54:S14-S20. (Pubitemid 30390610)
101. Bever CT, Young D, Anderson PM, et al. The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized placebo-controlled, double-blind, concentration controlled crossover trial. Neurology 1994;44:1054-1059. (Pubitemid 24188176)
102. VanDiemen HAM, Polman CH, Koetsier JC, et al. M. 4-Aminopyridine in patients with multiple sclerosis: dosage and serum level related efficacy and safety. Clin Neuropharmacol 1993;16:195-204. (Pubitemid 23149956)
103. Schwid SR, Petrie MD, McDermott MP, et al. Quantitative assessment of sustained release 4-aminopyridine for symptomatic treatment of multiple sclerosis. Neurology 1997;48:817-821.
104. Stork CM, Hoffman RS. Characterization of 4-aminopyridine in overdose. J Toxicol Clin Toxicol 1994;32:583-587. (Pubitemid 24332007)
105. Molgó J, Lundh H, Thesleff S. Potency of 3, 4-diaminopyridine and 4-aminopyridine on mammalian neuromuscular transmission and the effect of pH changes. Eur J Pharmacol 1980;61:25-34. (Pubitemid 10178022)
106. Lechat P, Deysson G, Lemeignan M, et al. Comparison of acute toxicity of some aminopyridines in vivo (mice) and in vitro (tissue culture) [Toxicité aigue composareé de quelques aminopyridines in vivo (souris) et in vitro (cultures cellulaires)]. Ann Pharm Fr 1968;26:345-349.
107. Lemeignan M, Millart H, Lamiable D, et al. Evaluation of 4-aminopyridine and 3, 4-diaminopyridine penetrability into cerebrospinal fluid in anesthetized rats. Brain Res 1984;304(1):166-169. (Pubitemid 14123328)
108. Flet L, Polard E, Guillard O, et al. 3, 4-diaminopyridine safety in clinical practice: an observational, retrospective cohort study. J Neurol 2010;257(6):937-946.
109. Bever CT, Katz E, Tierney D, et al. Experience with slow release 4-aminopyridine in multiple sclerosis patients: long-term tolerability and safety. J Neuroimmunol 1995;56-63(suppl 1):58.
110. Lundh H, Nilsson O, Rosén I, et al. Practical aspects of 3, 4-diaminopyridine treatment of the Lambert-Eaton myasthenic syndrome. Acta Neurol Scand 1993;88:136-140. (Pubitemid 23247977)
111. Open-label extension study to evaluate the safety, tolerability and activity of oral fampridine-SR. Available at: http://clinicaltrials.gov/ct2/ show/NCT00649792?term=nct00649792&rank=1. Accessed November 1, 2011.
112. Study of fampridine-SR tablets in multiple sclerosis patients who participated in the MS-F203 trial. Available at: http://clinicaltrials.gov/ct2/ show/NCT00648908?term=MS-f203&rank=1. Accessed November 1, 2011.
113. Open label extension study to evaluate the safety and tolerability of oral fampridine-SR in Canadian subjects with multiple sclerosis who participated in the Acorda extension trials. Available at: http://clinicaltrials.gov/ct2/ show/NCT01235221?term=fampridine&rank=8. Accessed November 1, 2011.