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Pharmacological activity and analytical methods for determination of fampridine – a drug for multiple sclerosis treatment

Author: 
Dobrina D Tsvetkova, Danka P Obreshkova and Petar Y Atanasov
Subject Area: 
Health Sciences
Abstract: 

Background: Multiple sclerosis is a chronic autoimmune disease of the central nervous system, characterized by inflammation, demyelinization and axonal injury. The current therapeutic strategies include: disease-modifying, immunomodulatory and immunosuppressive agents (Mitoxantrone). Immunomodulatory drugs are Interferon β, Glatiramer acetate, Leflunomide, Teriflunomide, Fingolimod, Laquinimod (with dual properties of immunomodulation and neuroprotection). For the treatment of relapsing-remitting and secondary progressive multiple sclerosis, new trend is the application of a specific therapeutic strategy with monoclonal antibodies: Alemtuzumab, Daclizumab, Natalizumab and Rituximab. Objective: The purpose of the study is the summarizing of the data for pharmacological activity and analytical methods for determination of a drug for treatment of multiple sclerosis – Fampridine. Methods: The method of literature survey of data for pharmacological action of Fampridine and analytical methods has been applied. Results: For pharmacological activity, literature survey has been shown, that 4-aminopyridine (Ampyra, Dalfampridine, Fampridine, Pymadine), as a selective voltage-dependent potassium channel blocker in the neuronal membrane, prolongs the depolarization phase of the action potential, improves axon potential propagation, increase neurotransmitter release at the neuromuscular junction. Fampridine has been used clinically for multiple sclerosis and Lambert-Eaton myasthenic syndrome. The combination Nivalin P: Galantamine hydrobromide/Pymadine is promising for Alzheimer's disease, due to the synergistic effect of cholinergic potentiation components: Galantamine hydrobromide as an acetylcholinesterase inhibitor and Pymadine as a stimulant of presynaptic release and synthesis of acetylcholine. For the analysis of related substances in 4-aminopyridine substance have been developed gradient HPLC method with UV-detection and capillary electrophoresis. For determination of 4-aminopyridine in capsules, serum and urine have been presented HPLC methods with UV-detection. For analysis of 4-aminopyridine in plasma capillary electrophoresis, spectrofluorimetry, gas chromatography with electron capture detector and HPLC with UV-detection have been described. Conclusion: The main pharmacological application of Fampridine is for treatment of multiple sclerosis and the combination Nivalin P: Galantamine hydrobromide/Pymadine is promising for Alzheimer's disease. As the most often applied methods for analysis of 4-aminopyridine in dosage forms and biological samples have been presented HPLC methods with UV-detection, gas chromatography and capillary electrophoresis.

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