N-0923, a novel soluble dopamine D2 agonist in the treatment of parkinsonism.
Identifieur interne : 005025 ( Ncbi/Merge ); précédent : 005024; suivant : 005026N-0923, a novel soluble dopamine D2 agonist in the treatment of parkinsonism.
Auteurs : V P Calabrese [États-Unis] ; K A Lloyd ; P. Brancazio ; E. Cefali ; P. Martin ; J. Wall ; D. SicaSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1998.
English descriptors
- KwdEn :
- Aged, Antiparkinson Agents (adverse effects), Antiparkinson Agents (pharmacokinetics), Antiparkinson Agents (therapeutic use), Dopamine Agonists (adverse effects), Dopamine Agonists (pharmacokinetics), Dopamine Agonists (therapeutic use), Dose-Response Relationship, Drug, Female, Humans, Infusion Pumps, Male, Metabolic Clearance Rate, Middle Aged, Neurologic Examination (drug effects), Parkinson Disease (drug therapy), Receptors, Dopamine D2 (agonists), Tetrahydronaphthalenes (adverse effects), Tetrahydronaphthalenes (pharmacokinetics), Tetrahydronaphthalenes (therapeutic use), Thiophenes (adverse effects), Thiophenes (pharmacokinetics), Thiophenes (therapeutic use).
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Dopamine Agonists, Tetrahydronaphthalenes, Thiophenes.
- chemical , agonists : Receptors, Dopamine D2.
- chemical , pharmacokinetics : Antiparkinson Agents, Dopamine Agonists, Tetrahydronaphthalenes, Thiophenes.
- chemical , therapeutic use : Antiparkinson Agents, Dopamine Agonists, Tetrahydronaphthalenes, Thiophenes.
- drug effects : Neurologic Examination.
- drug therapy : Parkinson Disease.
- Aged, Dose-Response Relationship, Drug, Female, Humans, Infusion Pumps, Male, Metabolic Clearance Rate, Middle Aged.
Abstract
N-0923, a novel aminotetralin dopamine D2 agonist, was shown to effectively reverse parkinsonian symptoms in nine dopa/agonist-responsive Parkinson's disease patients. The drug was given up to 4.5 hours by continuous intravenous (i.v.) infusion using an i.v. pump. The onset of anti-parkinsonian effect was seen within minutes of the initiation of the infusion and was absent within 90 minutes of cessation of the infusion. The short elimination half-life of N-0923 (90 min) would allow for the rapid initiation of drug effect when necessary and at the same time permit the effect to be terminated quickly if necessary. The drug would be useful in situations where oral medication is not feasible or is associated with erratic absorption. The patients tolerated the drug well. Dose escalation load was limited by nausea and vomiting. It should be noted that the doses were increased until these symptoms occurred, but therapeutic effects were noted well before the side effects occurred. Using a modified Columbia scale, maximum improvement consisted of a 27-95% drop in score. Maximum response was obtained at infusion rates varying from 2-16 microg/kg per hour and at blood levels of 0.11-1.49 microg/mL.
DOI: 10.1002/mds.870130503
PubMed: 9756144
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pubmed:9756144Le document en format XML
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Brancazio</name></author><author><name sortKey="Cefali, E" sort="Cefali, E" uniqKey="Cefali E" first="E" last="Cefali">E. Cefali</name></author><author><name sortKey="Martin, P" sort="Martin, P" uniqKey="Martin P" first="P" last="Martin">P. Martin</name></author><author><name sortKey="Wall, J" sort="Wall, J" uniqKey="Wall J" first="J" last="Wall">J. Wall</name></author><author><name sortKey="Sica, D" sort="Sica, D" uniqKey="Sica D" first="D" last="Sica">D. 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Brancazio</name></author><author><name sortKey="Cefali, E" sort="Cefali, E" uniqKey="Cefali E" first="E" last="Cefali">E. Cefali</name></author><author><name sortKey="Martin, P" sort="Martin, P" uniqKey="Martin P" first="P" last="Martin">P. Martin</name></author><author><name sortKey="Wall, J" sort="Wall, J" uniqKey="Wall J" first="J" last="Wall">J. Wall</name></author><author><name sortKey="Sica, D" sort="Sica, D" uniqKey="Sica D" first="D" last="Sica">D. Sica</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="1998" type="published">1998</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (pharmacokinetics)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Dopamine Agonists (adverse effects)</term><term>Dopamine Agonists (pharmacokinetics)</term><term>Dopamine Agonists (therapeutic use)</term><term>Dose-Response Relationship, Drug</term><term>Female</term><term>Humans</term><term>Infusion Pumps</term><term>Male</term><term>Metabolic Clearance Rate</term><term>Middle Aged</term><term>Neurologic Examination (drug effects)</term><term>Parkinson Disease (drug therapy)</term><term>Receptors, Dopamine D2 (agonists)</term><term>Tetrahydronaphthalenes (adverse effects)</term><term>Tetrahydronaphthalenes (pharmacokinetics)</term><term>Tetrahydronaphthalenes (therapeutic use)</term><term>Thiophenes (adverse effects)</term><term>Thiophenes (pharmacokinetics)</term><term>Thiophenes (therapeutic use)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Dopamine Agonists</term><term>Tetrahydronaphthalenes</term><term>Thiophenes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="agonists" xml:lang="en"><term>Receptors, Dopamine D2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antiparkinson Agents</term><term>Dopamine Agonists</term><term>Tetrahydronaphthalenes</term><term>Thiophenes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Dopamine Agonists</term><term>Tetrahydronaphthalenes</term><term>Thiophenes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Neurologic Examination</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>Dose-Response Relationship, Drug</term><term>Female</term><term>Humans</term><term>Infusion Pumps</term><term>Male</term><term>Metabolic Clearance Rate</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">N-0923, a novel aminotetralin dopamine D2 agonist, was shown to effectively reverse parkinsonian symptoms in nine dopa/agonist-responsive Parkinson's disease patients. The drug was given up to 4.5 hours by continuous intravenous (i.v.) infusion using an i.v. pump. The onset of anti-parkinsonian effect was seen within minutes of the initiation of the infusion and was absent within 90 minutes of cessation of the infusion. The short elimination half-life of N-0923 (90 min) would allow for the rapid initiation of drug effect when necessary and at the same time permit the effect to be terminated quickly if necessary. The drug would be useful in situations where oral medication is not feasible or is associated with erratic absorption. The patients tolerated the drug well. Dose escalation load was limited by nausea and vomiting. It should be noted that the doses were increased until these symptoms occurred, but therapeutic effects were noted well before the side effects occurred. Using a modified Columbia scale, maximum improvement consisted of a 27-95% drop in score. Maximum response was obtained at infusion rates varying from 2-16 microg/kg per hour and at blood levels of 0.11-1.49 microg/mL.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">9756144</PMID><DateCreated><Year>1999</Year><Month>01</Month><Day>05</Day></DateCreated><DateCompleted><Year>1999</Year><Month>01</Month><Day>05</Day></DateCompleted><DateRevised><Year>2006</Year><Month>11</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>13</Volume><Issue>5</Issue><PubDate><Year>1998</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. 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Dose escalation load was limited by nausea and vomiting. It should be noted that the doses were increased until these symptoms occurred, but therapeutic effects were noted well before the side effects occurred. Using a modified Columbia scale, maximum improvement consisted of a 27-95% drop in score. 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ValidYN="Y"><LastName>Sica</LastName><ForeName>D</ForeName><Initials>D</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><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="D018491">Dopamine Agonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017448">Receptors, Dopamine D2</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013764">Tetrahydronaphthalenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013876">Thiophenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>92206-54-7</RegistryNumber><NameOfSubstance UI="C047508">N 0437</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000368">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000978">Antiparkinson Agents</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000493">pharmacokinetics</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D018491">Dopamine Agonists</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000493">pharmacokinetics</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004305">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007260">Infusion Pumps</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008657">Metabolic Clearance Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008875">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009460">Neurologic Examination</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010300">Parkinson Disease</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017448">Receptors, Dopamine D2</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000819">agonists</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013764">Tetrahydronaphthalenes</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000493">pharmacokinetics</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013876">Thiophenes</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000493">pharmacokinetics</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1998</Year><Month>10</Month><Day>2</Day><Hour>2</Hour><Minute>3</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>3</Month><Day>28</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1998</Year><Month>10</Month><Day>2</Day><Hour>2</Hour><Minute>3</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">9756144</ArticleId><ArticleId IdType="doi">10.1002/mds.870130503</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Brancazio, P" sort="Brancazio, P" uniqKey="Brancazio P" first="P" last="Brancazio">P. Brancazio</name><name sortKey="Cefali, E" sort="Cefali, E" uniqKey="Cefali E" first="E" last="Cefali">E. Cefali</name><name sortKey="Lloyd, K A" sort="Lloyd, K A" uniqKey="Lloyd K" first="K A" last="Lloyd">K A Lloyd</name><name sortKey="Martin, P" sort="Martin, P" uniqKey="Martin P" first="P" last="Martin">P. Martin</name><name sortKey="Sica, D" sort="Sica, D" uniqKey="Sica D" first="D" last="Sica">D. Sica</name><name sortKey="Wall, J" sort="Wall, J" uniqKey="Wall J" first="J" last="Wall">J. Wall</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Calabrese, V P" sort="Calabrese, V P" uniqKey="Calabrese V" first="V P" last="Calabrese">V P Calabrese</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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