Need For Levodopa Research Articles

Attempts to obtain neuroprotection in Parkinson's disease.

It is suggested that oxidant stress is a contributing factor in the pathogenesis of Parkinson's disease (PD). Oxidant stress may contribute to cell death in PD because oxidative metabolism of dopamine has the potential to yield highly reactive and cytotoxic free radicals. Evidence for this hypothesis includes: (1) increased dopamine turnover with increased hydrogen peroxide formation; (2) decreased glutathione availability; and (3) increased reactive iron in the brains of patients with PD. Antioxidant therapies might be neuroprotective and could slow the clinical progression of the disease whereas metabolites of levodopa therapy may accelerate the rate of neuronal degeneration. Laboratory studies demonstrate that both selegiline and dopamine agonists can provide neuroprotective benefits. Selegiline-treated patients require less levodopa and have a delay in the progression of parkinsonian signs and symptoms. Dopamine agonists provide antiparkinson benefits and also diminish the need for levodopa.

Selegiline reduces need for levodopa in Parkinson??s disease

Selegiline reduces need for levodopa in Parkinson??s disease

Approval sought for first long-acting dopamine agonist in Parkinson??s disease

Cabergoline, already used successfully as a treatment for hyperprolactinaemic amenorrhoea and the inhibition of lactation, is now awaiting approval as a treatment for Parkinson’s disease. It is the first long-acting dopamine agonist to be developed for this indication. Treatment with cabergoline appears to delay the need for levodopa in newly diagnosed patients, and reduce the amount of levodopa necessary for symptom control in patients with more severe disease. It has also been used to reduce symptom severity in patients with levodopa-associated motor complications. Results of the studies used in the European license application were presented at the First Congress of the European Federation of Neurological Societies [ Marseilles, France; September 1995 ].

The Therapeutic Potential of Moclobemide, a Reversible Selective Monoamine Oxidase A Inhibitor in Parkinson's Disease

Dopamine is equally well deaminated oxidatively by monoamine oxidase (MAO) A and B types. Selegiline (L-deprenyl), a selective inhibitor of MAO-B, ameliorates the "wearing off" akinesia and delays the need for levodopa in mild, previously untreated Parkinson's disease. The therapeutic potential of selective inhibition of MAO-A in Parkinson's disease has not been examined in detail. MAO-A accounts for only about 20% of total MAO activity in the human basal ganglia, and it differs from MAO-B in distribution. In contrast to MAO-B, which is confined to the extraneuronal compartment, MAO-A is found both extraneuronally and within the presynaptic dopaminergic terminals. The inhibition of MAO-A might alter the intraneuronal handling of dopamine reuptaken from synaptic clefts and thereby prolong oral levodopa benefit. We have given moclobemide, a selective, reversible inhibitor of MAO-A, to nondepressed patients with Parkinson's disease receiving standard levodopa/peripheral decarboxylase inhibitor or levodopa with dopaminergic agonist (bromocriptine, pergolide). Selegiline was discontinued at least 8 weeks earlier. A standard oral levodopa challenge was performed at the patient's entry to the study and repeated on the 22nd day of moclobemide treatment (150 mg thrice daily). The overall time spent "on" and "off" before the onset of treatment and during the last week on the drug was estimated from the patients' diaries. Neuropsychological assessments were also made before and after 3 weeks of moclobemide to measure possible effects on cognitive performance and mood. In acute levodopa challenge, the latency of motor response was significantly shortened and its duration was prolonged during moclobemide treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of Parkinson's disease

The treatment of Parkinson's disease is reviewed. The rationale for using selegiline (deprenyl) as the first treatment in recently diagnosed patients is presented. Selegiline delays the need for levodopa; however, it is unclear whether this results from a symptomatic or a neuroprotective effect of selegiline. Levodopa combined with a decarboxylase inhibitor is the principal treatment for patients with moderate or marked symptoms. There is little evidence that levodopa has a deleterious effect on the court of Parkinson's disease. The relationship of levodopa to dyskinesias and response fluctuations is discussed. Pharmacokinetic and pharmacodynamic studies suggest that continuous dopaminergic stimulation may be superior to intermittent pulse therapy. The best approximation to continuous stimulation is the use of long-acting levodopa-carbidopa preparations supplemented by dopamine agonists.