Early introduction of dopamine agonists in the long-term treatment of Parkinson's disease. 1998

N Ogawa
Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Japan.

Recent efforts in treatment of Parkinson's disease (PD) have focused on the development of agents or strategies that suppress or delay disease progression and levodopa-induced adverse reactions. In the past decade, many reports have demonstrated advantages of the early introduction of a dopamine (DA) agonist or early combination therapy with a DA agonist and levodopa. In the search for available clinical information, most long-term studies of early treatment with a DA agonist have used bromocriptine. Although DA agonist monotherapy is effective for a majority of patients for a year or less, only a small proportion of patients (approximately 10%) obtain benefits for as long as 4-5 years. Those patients on long-term monotherapy with a DA agonist exhibited a few or no adverse reactions, such as the wearing-off phenomenon or dyskinesia. DA agonist monotherapy may avoid unnecessary levodopa administration to the special subpopulation of PD patients who have very slowly progressing disease and who can be maintained for the long-term on DA agonist monotherapy. In contrast to the high incidence of adverse reactions in patients receiving high-dose levodopa monotherapy, many trials have demonstrated that early combination therapy for PD using partial substitution of levodopa by bromocriptine can inhibit the development of motor fluctuations and/or dyskinesia. In these trials, good symptomatic effects with few adverse reactions were achieved by >25% substitution of levodopa by bromocriptine. In addition, in patients receiving bromocriptine plus levodopa therapy, disease progression appeared to be slowed for a few years. Although the mechanism by which the action of DA agonists combined with levodopa remains to be clarified, the lower incidence of levodopa-related adverse reactions in patients receiving early combination therapy suggests that continued use of a DA agonist is beneficial for patients with PD. In summary, because levodopa-induced adverse reactions can be reduced by combined use of a DA agonist with low-dose levodopa, introduction of a DA agonist at an early stage of PD, or with restricted use of additional levodopa, may be useful for long-term treatment of PD.

UI MeSH Term Description Entries
D010300 Parkinson Disease A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75) Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000978 Antiparkinson Agents Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists. Antiparkinson Drugs,Antiparkinsonian Agents,Antiparkinsonians,Agents, Antiparkinson,Agents, Antiparkinsonian,Drugs, Antiparkinson
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D018491 Dopamine Agonists Drugs that bind to and activate dopamine receptors. Dopamine Receptor Agonists,Dopaminergic Agonists,Agonists, Dopamine Receptor,Agonists, Dopaminergic,Dopamine Agonist,Dopamine Receptor Agonist,Dopaminergic Agonist,Receptor Agonists, Dopamine,Agonist, Dopamine,Agonist, Dopamine Receptor,Agonist, Dopaminergic,Agonists, Dopamine,Receptor Agonist, Dopamine

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