Sustained-Release Fampridine for Symptomatic Treatment of Multiple Sclerosis

Skaggs School of Pharmacy, The University of Montana, USA.
Annals of Pharmacotherapy (Impact Factor: 2.06). 10/2008; 42(10):1458-65. DOI: 10.1345/aph.1L028
Source: PubMed


To review the pharmacology, pharmacokinetics, clinical trials, and adverse effects of sustained-release (SR) fampridine in patients with multiple sclerosis (MS).
An English-language human data search was done using PubMed/MEDLINE (1966-August 2008) to retrieve relevant material using the search terms fampridine-SR, 4-aminopyridine, and multiple sclerosis. References of selected articles and information from the drug developer were used to further identify pertinent trials.
Article selection was based primarily on studies that evaluated the pharmacokinetics, safety, and efficacy of fampridine-SR in patients with MS. Relevant meeting abstracts were also included as part of the analysis.
Fampridine-SR is a sustained-release, orally administered potassium-channel blocker acting in the central nervous system to enhance conduction in demyelinated axons. Several small trials have evaluated the safety and efficacy of fampridine-SR in patients with MS to improve their walking ability. Data from a recent large Phase 3 trial indicated that walking speed improved in 42.9% of patients with MS who were treated with fampridine-SR compared with 9.3% of those who received placebo (p < 0.001). Treatment-related adverse events associated with the use of fampridine-SR include dizziness, insomnia, nausea, and paresthesia. More severe adverse events, such as seizure, have occurred in patients receiving doses higher than those currently recommended.
Positive results from 2 Phase 3 clinical trials have put fampridine-SR on the path toward approval as a medication for improving walking speed and lower extremity strength in patients with MS.

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    • "Additionally, they are advantageous because they have exhibited strong absorption and emission spectra and thus useful as fluorescent tags while investigating the activities on a target [7]. Aminopyridines are used as a drug for symptomatic treatment of multiple sclerosis by blocking potassium channels and prolonging action potentials [8] [9]. It has been used as intermediate for the synthesis of pharmaceutical agents such as piroxicam sulfapyridine, tenoxicam, and tripelennamine [6] [10]. "
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    ABSTRACT: 2-Aminopyridine (2-AP) and 2,6-diaminopyridine (2,6-DAP) are two derivatives of aminopyridines that act as an important organic intermediates, mostly used in medicines, dyes and organic sensors. The aim of the study was to evaluate the impact of biofield energy treatment on isotopic abundance ratios of 2 H/ 1 H, 13 C/ 12 C, or 15 N/ 14 N, in aminopyridine derivatives using gas chromatography-mass spectrometry (GC-MS). The 2-AP and 2,6-DAP samples were divided into two parts: control and treated. The control sample remained as untreated, while the treated sample was further divided into four groups as T1, T2, T3, and T4. The treated group was subjected to Mr. Trivedi's biofield energy treatment. The GC-MS spectra of 2-AP and 2,6-DAP showed five and six m/z peaks respectively due to the molecular ion peak and fragmented peaks of aminopyridine derivatives. The isotopic abundance ratio of 2 H/ 1 H, 13 C/ 12 C, or 15 N/ 14 N were calculated for both the derivatives and significant alteration was found in the treated samples as compared to the respective control. The isotopic abundance ratio of 2 H/ 1 H, 13 C/ 12 C, or 15 N/ 14 N in treated samples of 2-AP was decreased by 55.83% in T1 and significantly increased by 202.26% in T4. However, in case of 2,6-DAP, the isotopic abundance ratio of 2 H/ 1 H, 13 C/ 12 C, and 15 N/ 14 N, in the treated sample showed a significant increase (up to 370.54% in T3) with respect to the control. GC-MS data suggested that the biofield energy treatment on aminopyridine derivatives had significantly altered the isotopic abundance of 2 H, 13 C, or 15 N in the treated 2-AP and 2,6-DAP as compared to the control.
    Full-text · Dataset · Dec 2015
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    • "Aminopyridines are an important class of compounds used as a research tool for characterizing subtypes of the potassium channel [1]. 4-Aminopyridine or fampridine is used as a drug for symptomatic treatment of multiple sclerosis and it is believed to improve the walking in adults with several variations of the disease [1] [2]. It acts by blocking the potassium channels and prolong the action potentials, thereby releases neurotransmitters at the neuromuscular junction [3]. "
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    ABSTRACT: 2-Aminopyridine is an important compound, which is used as intermediate for the synthesis of pharmaceutical compounds. The present work was aimed to assess the effect of Mr. Trivedi's biofield energy treatment on the physical, thermal and spectral characteristics of 2-AP. The work was accomplished by dividing the sample in two parts i.e. one part was remained untreated, and another part had received biofield energy treatment. Subsequently, the samples were analyzed using various characterization techniques such as X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, ultra violet-visible spectroscopy, and Fourier transform infrared spectroscopy. The XRD analysis revealed a decrease in crystallite size of the treated sample (91.80 nm) as compared to the control sample (97.99 nm). Additionally, the result showed an increase in Bragg's angle (2θ) of the treated sample as compared to the control. The DSC and Differential thermal analysis analysis showed an increase in melting temperature of the treated 2-AP with respect to the control. Moreover, the latent heat of fusion of the treated sample was increased by 3.08%. The TGA analysis showed an increase in onset of thermal degradation (T onset), and maximum thermal decomposition temperature (T max) of the treated 2-AP as compared to the control sample. Additionally, the treated sample showed a reduction in weight loss as compared with the control indicating higher thermal stability of the sample. UV-visible analysis showed no changes in the absorption peak of the treated sample as compared to the control. The FT-IR spectroscopic results showed downward shifting of C-H stretching vibration 2991→2955 cm-1 in treated sample with respect to the control.
    Full-text · Dataset · Dec 2015
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    • ", such as 4 - aminopyridine , increase action potential duration and amplitude , leading to improved conduction in focally demyelinated axons . In this context , fampridine , a sustained release form of 4 - aminopyridine , has recently been put on the path toward approval as a medication for improving walking ability in a subgroup of MS patients ( Korenke et al . 2008 ; Bever and Judge 2009 ; Goodman et al . 2009 ) . These studies suggest that mis - targeting of axonal Kv channels may , as a disease enhancer , be a target for treatment ."
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    ABSTRACT: J. Neurochem. (2010) 114, 1243–1260. In multiple sclerosis, CNS demyelination is often followed by spontaneous repair, mostly achieved by adult oligodendrocyte precursor cells. Extent of this myelin repair differs, ranging from very low, limited to the plaque border, to extensive, with remyelination throughout the ‘shadow plaques.’ In addition to restoring neuronal connectivity, new myelin is neuroprotective. It reduces axonal loss and thus disability progression. Reciprocal communication between neurons and oligodendrocytes is essential for both myelin biogenesis and myelin repair. Hence, deciphering neuron-oligodendrocyte communication is not only important for understanding myelination per se, but also the pathophysiology that underlies demyelinating diseases and the development of innovative therapeutic strategies.
    Full-text · Article · Sep 2010 · Journal of Neurochemistry
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