Comparison of the clinical pharmacology of (-)NPA and levodopa in Parkinson's disease.
Identifieur interne : 000058 ( Pmc/Curation ); précédent : 000057; suivant : 000059Comparison of the clinical pharmacology of (-)NPA and levodopa in Parkinson's disease.
Auteurs : M Mouradian ; I Heuser ; F. Baronti ; M. Giuffra ; K. Conant ; T Davis ; T ChaseSource :
- Journal of Neurology, Neurosurgery, and Psychiatry [ 0022-3050 ] ; 1991.
Abstract
Direct acting dopamine agonists are generally less effective than levodopa in relieving symptoms of Parkinson's disease. In an attempt to quantitate and explain this situation, the acute motor responses to intravenous injections of the dopamine agonist, (-)-N-n-propyl-norapomorphine hydrochloride (NPA), were compared with those of the dopamine precursor, levodopa. At optimum dose levels, the acute anti-Parkinsonian efficacy of NPA averaged only about 50% of maximum, while essentially total symptom suppression was obtained with levodopa in patients previously treated with the amine precursor. Dyskinesia severity, however, was similar with the two drugs. These differences in anti-Parkinsonian efficacy may reflect the fact that while NPA acts mainly on D-2 dopamine receptors, levodopa results in stimulation of both the D-1 and D-2 subsets of receptors at a more physiological ratio. Future efforts to develop dopamine agonists for the treatment of Parkinsonian symptoms may thus have to consider focusing on drugs having pharmacological profile more similar to that of dopamine.
Url:
PubMed: 1865201
PubMed Central: 488537
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<author><name sortKey="Mouradian, M M" sort="Mouradian, M M" uniqKey="Mouradian M" first="M" last="Mouradian">M Mouradian</name>
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<author><name sortKey="Heuser, I J" sort="Heuser, I J" uniqKey="Heuser I" first="I" last="Heuser">I Heuser</name>
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<author><name sortKey="Baronti, F" sort="Baronti, F" uniqKey="Baronti F" first="F" last="Baronti">F. Baronti</name>
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<author><name sortKey="Conant, K" sort="Conant, K" uniqKey="Conant K" first="K" last="Conant">K. Conant</name>
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<author><name sortKey="Davis, T L" sort="Davis, T L" uniqKey="Davis T" first="T" last="Davis">T Davis</name>
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<author><name sortKey="Chase, T N" sort="Chase, T N" uniqKey="Chase T" first="T" last="Chase">T Chase</name>
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<front><div type="abstract" xml:lang="en"><p>Direct acting dopamine agonists are generally less effective than levodopa in relieving symptoms of Parkinson's disease. In an attempt to quantitate and explain this situation, the acute motor responses to intravenous injections of the dopamine agonist, (-)-N-n-propyl-norapomorphine hydrochloride (NPA), were compared with those of the dopamine precursor, levodopa. At optimum dose levels, the acute anti-Parkinsonian efficacy of NPA averaged only about 50% of maximum, while essentially total symptom suppression was obtained with levodopa in patients previously treated with the amine precursor. Dyskinesia severity, however, was similar with the two drugs. These differences in anti-Parkinsonian efficacy may reflect the fact that while NPA acts mainly on D-2 dopamine receptors, levodopa results in stimulation of both the D-1 and D-2 subsets of receptors at a more physiological ratio. Future efforts to develop dopamine agonists for the treatment of Parkinsonian symptoms may thus have to consider focusing on drugs having pharmacological profile more similar to that of dopamine.</p>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Neurol Neurosurg Psychiatry</journal-id>
<journal-title>Journal of Neurology, Neurosurgery, and Psychiatry</journal-title>
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<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
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<title-group><article-title>Comparison of the clinical pharmacology of (-)NPA and levodopa in Parkinson's disease.</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Mouradian</surname>
<given-names>M M</given-names>
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<contrib contrib-type="author"><name><surname>Heuser</surname>
<given-names>I J</given-names>
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<contrib contrib-type="author"><name><surname>Baronti</surname>
<given-names>F</given-names>
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<contrib contrib-type="author"><name><surname>Giuffra</surname>
<given-names>M</given-names>
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<contrib contrib-type="author"><name><surname>Conant</surname>
<given-names>K</given-names>
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<contrib contrib-type="author"><name><surname>Davis</surname>
<given-names>T L</given-names>
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<contrib contrib-type="author"><name><surname>Chase</surname>
<given-names>T N</given-names>
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<aff>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.</aff>
<pub-date pub-type="ppub"><month>5</month>
<year>1991</year>
</pub-date>
<volume>54</volume>
<issue>5</issue>
<fpage>401</fpage>
<lpage>405</lpage>
<abstract><p>Direct acting dopamine agonists are generally less effective than levodopa in relieving symptoms of Parkinson's disease. In an attempt to quantitate and explain this situation, the acute motor responses to intravenous injections of the dopamine agonist, (-)-N-n-propyl-norapomorphine hydrochloride (NPA), were compared with those of the dopamine precursor, levodopa. At optimum dose levels, the acute anti-Parkinsonian efficacy of NPA averaged only about 50% of maximum, while essentially total symptom suppression was obtained with levodopa in patients previously treated with the amine precursor. Dyskinesia severity, however, was similar with the two drugs. These differences in anti-Parkinsonian efficacy may reflect the fact that while NPA acts mainly on D-2 dopamine receptors, levodopa results in stimulation of both the D-1 and D-2 subsets of receptors at a more physiological ratio. Future efforts to develop dopamine agonists for the treatment of Parkinsonian symptoms may thus have to consider focusing on drugs having pharmacological profile more similar to that of dopamine.</p>
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