Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease.
Identifieur interne : 004646 ( PubMed/Curation ); précédent : 004645; suivant : 004647Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease.
Auteurs : J. Lyytinen [Finlande] ; S. Kaakkola ; S. Ahtila ; P. Tuomainen ; H. Ter V InenSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1997.
English descriptors
- KwdEn :
- Aged, Analysis of Variance, Antiparkinson Agents (pharmacology), Antiparkinson Agents (therapeutic use), Benserazide (diagnostic use), Catechol O-Methyltransferase Inhibitors, Catechols (pharmacology), Catechols (therapeutic use), Cross-Over Studies, Double-Blind Method, Drug Interactions, Drug Therapy, Combination, Enzyme Inhibitors (pharmacology), Enzyme Inhibitors (therapeutic use), Female, Humans, Levodopa (pharmacokinetics), Levodopa (therapeutic use), Male, Middle Aged, Monoamine Oxidase Inhibitors (pharmacology), Monoamine Oxidase Inhibitors (therapeutic use), Motor Activity (drug effects), Nitriles, Parkinson Disease (blood), Parkinson Disease (drug therapy), Selegiline (pharmacology), Selegiline (therapeutic use).
- MESH :
- chemical , diagnostic use : Benserazide.
- chemical , pharmacokinetics : Levodopa.
- chemical , pharmacology : Antiparkinson Agents, Catechols, Enzyme Inhibitors, Monoamine Oxidase Inhibitors, Selegiline.
- chemical , therapeutic use : Antiparkinson Agents, Catechols, Enzyme Inhibitors, Levodopa, Monoamine Oxidase Inhibitors, Selegiline.
- blood : Parkinson Disease.
- drug effects : Motor Activity.
- drug therapy : Parkinson Disease.
- Aged, Analysis of Variance, Catechol O-Methyltransferase Inhibitors, Cross-Over Studies, Double-Blind Method, Drug Interactions, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Nitriles.
Abstract
The effect of selegiline (L-deprenyl) on plasma catecholamines, clinical response, and drug tolerability was studied in 13 patients with Parkinson's disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral catechol-O-methyltransferase (COMT) inhibitor, in a placebo-controlled double-blind study. An L-Dopa test was performed on 3 study days. The first study day was with L-Dopa/benserazide only (control), the second after 14 days of treatment with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination with either selegiline (10 mg daily) or placebo. After a 2-week washout period, selegiline and placebo treatments were switched, and the third study day was after 14 days of treatment. During the study days, clinical response was evaluated at 30-min intervals for 6 h, by using the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS). In addition, repeated blood pressure measurements were made, and plasma samples were taken for analysis of L-Dopa, 3-O-methyldopa (3-OMD), dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA), dopamine, noradrenaline, and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG). Monoamine oxidase B (MAO-B) and COMT enzyme activities were measured from platelets and erythrocytes, respectively. Entacapone improved the clinical response to L-Dopa during both selegiline and placebo (p < 0.001) treatments. The improvement was more marked during combined selegiline and entacapone treatment than with entacapone alone (p < 0.01). Entacapone significantly increased plasma L-Dopa and DOPAC levels and decreased plasma 3-OMD and MHPG levels both with selegiline and placebo. Selegiline partially inhibited the entacapone-induced increase of plasma DOPAC. Plasma dopamine and noradrenaline levels did not change. Entacapone decreased erythrocyte COMT activity by > 35% (p < 0.001), and platelet MAO-B activity was almost completely inhibited by selegiline (p < 0.001). One patient withdrew because of diarrhea, dizziness, and loss of sleep when receiving selegiline treatment. Otherwise no differences in adverse events, mean daily blood pressures, or other safety parameters were observed between selegiline and placebo treatments. Our results suggest that entacapone can be safely administered together with L-Dopa and selegiline in patients with PD, although further studies with larger number of patients and longer treatment periods are necessary to confirm this finding.
DOI: 10.1002/mds.870120404
PubMed: 9251066
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Tuomainen</name></author><author><name sortKey="Ter V Inen, H" sort="Ter V Inen, H" uniqKey="Ter V Inen H" first="H" last="Ter V Inen">H. Ter V Inen</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1997">1997</date><idno type="RBID">pubmed:9251066</idno><idno type="pmid">9251066</idno><idno type="doi">10.1002/mds.870120404</idno><idno type="wicri:Area/PubMed/Corpus">004646</idno><idno type="wicri:Area/PubMed/Curation">004646</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease.</title><author><name sortKey="Lyytinen, J" sort="Lyytinen, J" uniqKey="Lyytinen J" first="J" last="Lyytinen">J. Lyytinen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University of Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Neurology, University of Helsinki</wicri:regionArea></affiliation></author><author><name sortKey="Kaakkola, S" sort="Kaakkola, S" uniqKey="Kaakkola S" first="S" last="Kaakkola">S. Kaakkola</name></author><author><name sortKey="Ahtila, S" sort="Ahtila, S" uniqKey="Ahtila S" first="S" last="Ahtila">S. Ahtila</name></author><author><name sortKey="Tuomainen, P" sort="Tuomainen, P" uniqKey="Tuomainen P" first="P" last="Tuomainen">P. Tuomainen</name></author><author><name sortKey="Ter V Inen, H" sort="Ter V Inen, H" uniqKey="Ter V Inen H" first="H" last="Ter V Inen">H. Ter V Inen</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="1997" type="published">1997</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Analysis of Variance</term><term>Antiparkinson Agents (pharmacology)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Benserazide (diagnostic use)</term><term>Catechol O-Methyltransferase Inhibitors</term><term>Catechols (pharmacology)</term><term>Catechols (therapeutic use)</term><term>Cross-Over Studies</term><term>Double-Blind Method</term><term>Drug Interactions</term><term>Drug Therapy, Combination</term><term>Enzyme Inhibitors (pharmacology)</term><term>Enzyme Inhibitors (therapeutic use)</term><term>Female</term><term>Humans</term><term>Levodopa (pharmacokinetics)</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Middle Aged</term><term>Monoamine Oxidase Inhibitors (pharmacology)</term><term>Monoamine Oxidase Inhibitors (therapeutic use)</term><term>Motor Activity (drug effects)</term><term>Nitriles</term><term>Parkinson Disease (blood)</term><term>Parkinson Disease (drug therapy)</term><term>Selegiline (pharmacology)</term><term>Selegiline (therapeutic use)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Benserazide</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiparkinson Agents</term><term>Catechols</term><term>Enzyme Inhibitors</term><term>Monoamine Oxidase Inhibitors</term><term>Selegiline</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Catechols</term><term>Enzyme Inhibitors</term><term>Levodopa</term><term>Monoamine Oxidase Inhibitors</term><term>Selegiline</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Motor Activity</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Analysis of Variance</term><term>Catechol O-Methyltransferase Inhibitors</term><term>Cross-Over Studies</term><term>Double-Blind Method</term><term>Drug Interactions</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Nitriles</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The effect of selegiline (L-deprenyl) on plasma catecholamines, clinical response, and drug tolerability was studied in 13 patients with Parkinson's disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral catechol-O-methyltransferase (COMT) inhibitor, in a placebo-controlled double-blind study. An L-Dopa test was performed on 3 study days. The first study day was with L-Dopa/benserazide only (control), the second after 14 days of treatment with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination with either selegiline (10 mg daily) or placebo. After a 2-week washout period, selegiline and placebo treatments were switched, and the third study day was after 14 days of treatment. During the study days, clinical response was evaluated at 30-min intervals for 6 h, by using the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS). In addition, repeated blood pressure measurements were made, and plasma samples were taken for analysis of L-Dopa, 3-O-methyldopa (3-OMD), dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA), dopamine, noradrenaline, and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG). Monoamine oxidase B (MAO-B) and COMT enzyme activities were measured from platelets and erythrocytes, respectively. Entacapone improved the clinical response to L-Dopa during both selegiline and placebo (p < 0.001) treatments. The improvement was more marked during combined selegiline and entacapone treatment than with entacapone alone (p < 0.01). Entacapone significantly increased plasma L-Dopa and DOPAC levels and decreased plasma 3-OMD and MHPG levels both with selegiline and placebo. Selegiline partially inhibited the entacapone-induced increase of plasma DOPAC. Plasma dopamine and noradrenaline levels did not change. Entacapone decreased erythrocyte COMT activity by > 35% (p < 0.001), and platelet MAO-B activity was almost completely inhibited by selegiline (p < 0.001). One patient withdrew because of diarrhea, dizziness, and loss of sleep when receiving selegiline treatment. Otherwise no differences in adverse events, mean daily blood pressures, or other safety parameters were observed between selegiline and placebo treatments. Our results suggest that entacapone can be safely administered together with L-Dopa and selegiline in patients with PD, although further studies with larger number of patients and longer treatment periods are necessary to confirm this finding.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">9251066</PMID><DateCreated><Year>1997</Year><Month>10</Month><Day>14</Day></DateCreated><DateCompleted><Year>1997</Year><Month>10</Month><Day>14</Day></DateCompleted><DateRevised><Year>2014</Year><Month>11</Month><Day>20</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>12</Volume><Issue>4</Issue><PubDate><Year>1997</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>497-505</MedlinePgn></Pagination><Abstract><AbstractText>The effect of selegiline (L-deprenyl) on plasma catecholamines, clinical response, and drug tolerability was studied in 13 patients with Parkinson's disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral catechol-O-methyltransferase (COMT) inhibitor, in a placebo-controlled double-blind study. An L-Dopa test was performed on 3 study days. The first study day was with L-Dopa/benserazide only (control), the second after 14 days of treatment with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination with either selegiline (10 mg daily) or placebo. After a 2-week washout period, selegiline and placebo treatments were switched, and the third study day was after 14 days of treatment. During the study days, clinical response was evaluated at 30-min intervals for 6 h, by using the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS). In addition, repeated blood pressure measurements were made, and plasma samples were taken for analysis of L-Dopa, 3-O-methyldopa (3-OMD), dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA), dopamine, noradrenaline, and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG). Monoamine oxidase B (MAO-B) and COMT enzyme activities were measured from platelets and erythrocytes, respectively. Entacapone improved the clinical response to L-Dopa during both selegiline and placebo (p < 0.001) treatments. The improvement was more marked during combined selegiline and entacapone treatment than with entacapone alone (p < 0.01). Entacapone significantly increased plasma L-Dopa and DOPAC levels and decreased plasma 3-OMD and MHPG levels both with selegiline and placebo. Selegiline partially inhibited the entacapone-induced increase of plasma DOPAC. Plasma dopamine and noradrenaline levels did not change. Entacapone decreased erythrocyte COMT activity by > 35% (p < 0.001), and platelet MAO-B activity was almost completely inhibited by selegiline (p < 0.001). One patient withdrew because of diarrhea, dizziness, and loss of sleep when receiving selegiline treatment. Otherwise no differences in adverse events, mean daily blood pressures, or other safety parameters were observed between selegiline and placebo treatments. Our results suggest that entacapone can be safely administered together with L-Dopa and selegiline in patients with PD, although further studies with larger number of patients and longer treatment periods are necessary to confirm this finding.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lyytinen</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, University of Helsinki, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kaakkola</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Ahtila</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Tuomainen</LastName><ForeName>P</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Teräväinen</LastName><ForeName>H</ForeName><Initials>H</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016430">Clinical Trial</PublicationType><PublicationType UI="D018848">Controlled Clinical Trial</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>UNITED STATES</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D065098">Catechol O-Methyltransferase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002396">Catechols</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004791">Enzyme Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008996">Monoamine Oxidase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009570">Nitriles</NameOfSubstance></Chemical><Chemical><RegistryNumber>14611-51-9</RegistryNumber><NameOfSubstance UI="D012642">Selegiline</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical><Chemical><RegistryNumber>4975G9NM6T</RegistryNumber><NameOfSubstance UI="C071192">entacapone</NameOfSubstance></Chemical><Chemical><RegistryNumber>762OS3ZEJU</RegistryNumber><NameOfSubstance UI="D001545">Benserazide</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000368">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000704">Analysis of Variance</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000978">Antiparkinson Agents</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D001545">Benserazide</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000176">diagnostic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y" UI="D065098">Catechol O-Methyltransferase Inhibitors</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002396">Catechols</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D018592">Cross-Over Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004311">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004347">Drug Interactions</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004359">Drug Therapy, Combination</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004791">Enzyme Inhibitors</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007980">Levodopa</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000493">pharmacokinetics</QualifierName><QualifierName MajorTopicYN="N" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008875">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008996">Monoamine Oxidase Inhibitors</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009043">Motor Activity</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009570">Nitriles</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010300">Parkinson Disease</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000097">blood</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D012642">Selegiline</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1997</Year><Month>7</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1997</Year><Month>7</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1997</Year><Month>7</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">9251066</ArticleId><ArticleId IdType="doi">10.1002/mds.870120404</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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