Madopar Review Article
Madopar is a medicine used for treating different forms of Parkinson’s diseases, except drug-induced Parkinsonism. Comprising two active ingredients called levodopa and benserazide, Madopar is categorized under group of medicines known as antiparkinsonian agents. It is available in the market under the brand name Madopar in UK and Prolopa in Canada, and both are manufactured by Roche.
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How to Fight Parkinson Disease?
Levodopa and benserazide commonly known as Madopar belong to the group of antiparkinsonian agents. Casimir Funk, a polish biochemist, was the first person ever to synthesize levodopa in 1911. However, the substance became well-known only by the mid of the 20th century, in 1967, when it was first used in clinical practice. The first large study reporting improvements of Parkinson’s disease following the treatment with levodopa was held by George C. Cotzias and it was documented and published in 1968. It was a revolution in the treatment of Parkinson’s disease or PD. In 1997, the FDA approved levodopa for clinical use.
Madopar is considered to be the most effective of all antiparkinsonian agents and it is used as a basic therapy in Parkinson Disease (PD). Levodopa enhances the production of the necessary dopamine in the nerve cells thus reducing its deficit in the brain. Moreover, Levodopa eliminates hypokinesia, rigidity, tremor, dysphagia, and drooling. Levodopa converts into dopamine in the central nervous system and therefore the result is an antiparkinsonian action by providing dopamine and thus supplementing it in the CNS. Dopamine, which is formed in peripheral tissues, doesn’t reach CNS and consequently doesn’t have the desired antiparkinsonian effect. It is also responsible for most of PD’s side effects. Benserazide - an inhibitor of peripheral dopa-decarboxylase - reduces the formation of dopamine in the peripheral tissues which indirectly leads to increased amounts of levodopa entering the CNS.
The proportion of levodopa and benserazide in Madopar is 4:1. Benserazide is as effective as levodopa but it is prescribed in smaller doses and has better acceptability. A pronounced therapeutic effect is only observed after 6-8 days (maximum 25-30 days) from the start of the treatment with Madopar. The adequate function of these drugs can maintain the stable treatment efficiency for 7 years or more while maintaining the quality of life and increasing life span.
Madopar HBS (hydrodynamically balanced system) is a new step in PD therapy. Its active substance is released in the gastrointestinal tract and it provides a prolonged effect (up to 8 hours). This kind of Madopar drug is prescribed to reduce night and early morning Parkinson symptoms and improve the quality of life in general. It is especially indicated and efficient in cases when patients lack an evening dose of traditional levodopa (Illarioshkin, 2004).
Evaluation of the clinical effectiveness of this drug, including the impact on the quality of life and its safety, proved its high efficiency (Boiko, 2004).
Here is an example of clinical trial performed by B. O. Williams and D. Carlyle (1979). A nine-month clinical trial of Madopar treatment was carried out on 20 elderly patients with PD to show effectiveness and acceptability. Every month, daily activities were monitored to show the effects of the treatment. Fundamental enhancement was monitored in the first month and significant improvement was reached by the end of the 3 month treatment. Akinesia and rigidity improved in the majority of patients. The treatment proved acceptability and side-effects were not worrying.
Another study was held by C. Pacchetti, E. Martignoni, L. Sibilla, P Bruggi, M. Turla, G. Nappi (1990). An open clinical trial studied 25 patients with PD, who suffered fluctuation. In this study, Madopar HBS was taken together with Madopar standard. The follow-up period was 24 months. As a result, nocturnal and early morning akinesia and predictable fluctuations improved for the whole treatment period without the dosage being changed. The study shows that this kind of treatment produces a long-term effect and acceptability in patients with PD who suffer fluctuation.
One more study was held by T. Caraceni, N. Nordera, E. Lamperti and A. Lorizio. 23 patients with PD, suffering fluctuations and abnormal involuntary movements (11 men and 12 women), aged between 62 and 72 years took part in a 120 days study. They substituted standard Madopar with Madopar HBS (hydro dynamically balanced system). Al the patients have been suffering from this disease for about 16-22 years and were severely disabled (Hoehn and Yahr grade III–V). The results were the following:
- 47% of patients showed improvements in fluctuations;
- 54% reported improvements in PD symptoms
- 33% showed improvements in abnormal involuntary movements.
Madopar is considered to be the most effective antiparkinsonian agent. This was proved by various clinical studies. If taken properly, Madopar and Madopar HBS reduce parkinsonian symptoms, fluctuations and abnormal involuntary movements. In most cases, it also improves hypokinesia, rigidity, tremor, dysphagia and drooling.
Fahn S, 2008, "The history of dopamine and levodopa in the treatment of Parkinson's disease” in Movement Disorder, Copyright, WI, USA, pp. 497–508.
Hornykiewicz O, 2002 "L-DOPA: from a biologically inactive amino acid to a successful therapeutic agent", Amino Acids, University of Vienna, Vienna, Austria. pp.65–70.
Cotzias, G 1968, “ L-Dopa for Parkinsonism”, New England Journal of Medicine, New England.
Illarioshkin S.N., 2004, “The main principles of PD treatment”, Russian medical journal, Russia, pp.604-608.
B. O. Williams and D. Carlyle. “Levodopa/benserazide (‘Madopar’) combination therapy in elderly patients with parkinsonism”, Current Medicine Response Opinion, USA, pp. 1-7.
C Pacchetti, E Martignoni, L Sibilla, P Bruggi, M Turla and G Nappi “Effectiveness of Madopar HBS plus Madopar standard in patients with fluctuating Parkinson's disease: two years of follow-up”, European Neurology, Switzerland, Basel, pp.319-323
T. Caraceni, N. Nordera, E. Lamperti and A. Lorizio “The Italian Journal of Neurological Sciences” Italy, pp.407-414
Madopar Review Article