4-Aminopyridine Is Superior to 3,4-Diaminopyridine in the Treatment of Patients With Multiple Sclerosis

Polman, Chris H.; Bertelsmann, F.W.; Waal, Reneé de; Diemen, H.A.M. van; Uitdehaag, Bernard M. J.; Loenen, A. C. Van; Koetsier, J.C.

doi:10.1001/archneur.1994.00540230074016

Cited by 53 publications

(38 citation statements)

References 11 publications

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“…Nevertheless, it is still unresolved whether 4-AP/SR-AP has an effect on fatigue. A small effect on fatigue has been reported [Polman et al 1994a[Polman et al , 1994bRomani et al 2004;Rossini et al 2001] but Goodman and colleagues did not find a significant effect of SR-AP on fatigue in a large high-quality trial [Goodman et al 2007]. …”

Section: Discussionmentioning

confidence: 99%

“…Bostock and colleagues examined the spinal roots of rats, where they also found that 4-AP can increase peak amplitudes in C fibres and abolish late phase outward potassium current and raise blocking temperatures in demyelinated fibres [Bostock et al 1981 Analysis is based on Davis et al 1990;Stefoski et al 1991;Van Diemen et al 1992;Van Diemen et al 1993a;Polman et al 1994a;Polman et al 1994b;Bever et al1994;Smits et al 1994 andRomani et al 2004. transient potassium current I A involves two kinds of effects. In the presence of aminopyridine, time to peak current during a depolarization is shortened and the initial rate of fall of current is hastened.…”

Section: Experimental Studies Including Animal Studiesmentioning

confidence: 99%

“…However, some trials were open label [Jones et al 1983;Polman et al 1994b] or single blinded [Stefoski et al 1987]. A substantial amount of the included trials have relatively small sample sizes ranging from 8 to 36 [Bever et al 1994;Davis et al 1990;Goodman et al 2007;Jones et al 1983;Polman et al 1994aPolman et al , 1994bSchwid et al 1997;Smits et al 1994;Stefoski et al 1987Stefoski et al , 1991. Nonetheless all studies point in the direction of a positive clinical effect of 4-AP/SR-AP with the exception of Smits and colleagues [Smits et al 1994].…”

Section: Clinical Trials With Clinical Endpointsmentioning

confidence: 99%

“…They demonstrated that 4-AP is superior to DAP in the treatment of patients with MS [Polman et al 1994a]. …”

Section: Immediate-release 4-aminopyridinementioning

confidence: 99%

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4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review

Jensen

Ravnborg

Dalgas

2013

Ther Adv Neurol Disord

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This systematic review summarizes the existing evidence on the effect of 4-aminopyridine (4-AP) as a symptomatic treatment of decreased walking capacity in patients with multiple sclerosis (MS) when administered as an immediate release compound and a slow release compound. It summarizes existing evidence on the basic mechanisms of 4-AP from experimental studies and evidence on the clinical use of the compound. A systematic literature search was conducted of the following databases: PubMed and EMBASE. Thirty-five studies were included in the review divided into 16 experimental studies, two clinical studies with paraclinical endpoints and 17 clinical studies with clinical endpoints. Animal studies show that 4-AP can improve impulse conduction through demyelinated lesions. In patients with MS this translates into improved walking speed and muscle strength of the lower extremities in a subset of patients at a level that is often of clinical relevance. Phase III trials demonstrate approximately 25% increase in walking speed in roughly 40% and improved muscle strength in the lower extremities. Furthermore, 4-AP might have an effect on other domains such as cognition, upper extremity function and bowel and bladder, but this warrants further investigation. Side effects are mainly mild to moderate, consisting primarily of paraesthesia, dizziness, nausea/vomiting, falls/balance disorders, insomnia, urinary tract infections and asthenia. Side effects are worse when administered intravenously and when administered as an immediate release compound. Serious adverse events are rarely seen in the marketed clinical dosages. In conclusion, 4-AP is easy and safe to use. Slow release 4-AP shows more robust clinical effects and a more beneficial side-effect profile than immediate release 4-AP.

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Section: Discussionmentioning

confidence: 99%

Section: Experimental Studies Including Animal Studiesmentioning

confidence: 99%

Section: Clinical Trials With Clinical Endpointsmentioning

confidence: 99%

“…They demonstrated that 4-AP is superior to DAP in the treatment of patients with MS [Polman et al 1994a]. …”

Section: Immediate-release 4-aminopyridinementioning

confidence: 99%

See 2 more Smart Citations

4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review

Jensen

Ravnborg

Dalgas

2013

Ther Adv Neurol Disord

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show abstract

“…Similar to neurotrauma, multiple sclerosis has a long history of clinical testing of 4-AP [50][51][52][53][54][55][56][57][58][59][60][61] . Recently, a series of carefully designed clinical trials have provided significant improvement in walking ability of multiple sclerosis patients [43,[62][63][64] .…”

Section: The Effects Of 4-ap In Human Testingmentioning

confidence: 99%

Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons

Shi

Sun

2011

Neurosci. Bull.

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Most axons in the vertebral central nervous system are myelinated by oligodendrocytes. Myelin protects and insulates neuronal processes, enabling the fast, saltatory conduction unique to myelinated axons. Myelin disruption resulting from trauma and biochemical reaction is a common pathological event in spinal cord injury and chronic neurodegenerative diseases. Myelin damage-induced axonal conduction block is considered to be a significant contributor to the devastating neurological deficits resulting from trauma and illness. Potassium channels are believed to play an important role in axonal conduction failure in spinal cord injury and multiple sclerosis. Myelin damage has been shown to unmask potassium channels, creating aberrant potassium currents that inhibit conduction. Potassium channel blockade reduces this ionic leakage and improves conduction. The present review was mainly focused on the development of this technique of restoring axonal conduction and neurological function of demyelinated axons. The drug 4-aminopyridine has recently shown clinical success in treating multiple sclerosis symptoms. Further translational research has also identified several novel potassium channel blockers that may prove effective in restoring axonal conduction.

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Aminopyridines for symptomatic treatment in multiple sclerosis

Solari

Uitdehaag

Giuliani

et al. 2002

Cochrane Database of Systematic Reviews

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4-Aminopyridine Is Superior to 3,4-Diaminopyridine in the Treatment of Patients With Multiple Sclerosis

Cited by 53 publications

References 11 publications

4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review

4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review

Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons

Aminopyridines for symptomatic treatment in multiple sclerosis

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