Effect of the putative dopamine D1 agonist and D2 antagonist FCE 23884 on Parkinson's disease.
Identifieur interne : 004834 ( PubMed/Checkpoint ); précédent : 004833; suivant : 004835Effect of the putative dopamine D1 agonist and D2 antagonist FCE 23884 on Parkinson's disease.
Auteurs : L V Metman [États-Unis] ; P J Blanchet ; D. De Jong ; M M Mouradian ; T N ChaseSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1996.
English descriptors
- KwdEn :
- Aged, Antiparkinson Agents (adverse effects), Antiparkinson Agents (therapeutic use), Carbidopa (adverse effects), Carbidopa (therapeutic use), Dopamine Agonists (administration & dosage), Dopamine Agonists (therapeutic use), Dopamine Antagonists (adverse effects), Dopamine Antagonists (therapeutic use), Dopamine D2 Receptor Antagonists, Double-Blind Method, Drug Therapy, Combination, Ergolines (adverse effects), Ergolines (therapeutic use), Female, Humans, Levodopa (adverse effects), Levodopa (therapeutic use), Male, Middle Aged, Neurologic Examination (drug effects), Parkinson Disease (drug therapy), Parkinson Disease (physiopathology), Receptors, Dopamine D1 (drug effects), Receptors, Dopamine D1 (physiology), Receptors, Dopamine D2 (physiology), Treatment Outcome.
- MESH :
- chemical , administration & dosage : Dopamine Agonists.
- chemical , adverse effects : Antiparkinson Agents, Carbidopa, Dopamine Antagonists, Ergolines, Levodopa.
- chemical , drug effects : Receptors, Dopamine D1.
- chemical , physiology : Receptors, Dopamine D1, Receptors, Dopamine D2.
- chemical , therapeutic use : Antiparkinson Agents, Carbidopa, Dopamine Agonists, Dopamine Antagonists, Ergolines, Levodopa.
- drug effects : Neurologic Examination.
- drug therapy : Parkinson Disease.
- physiopathology : Parkinson Disease.
- Aged, Dopamine D2 Receptor Antagonists, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Treatment Outcome.
Abstract
The ergoline derivative FCE 23,884 acts as a dopamine D1 agonist in untreated parkinsonian animals and as a D2 antagonist in animals whose dopamine system is intact or levodopa treated. To evaluate whether this dual action might benefit patients with Parkinson's disease (PD) who have developed levodopa-induced dyskinesias, the motor effects of FCE 23,884 were examined in seven such individuals using a double-blind, placebo-controlled design. At doses up to the maximum tolerated dose (3.5 +/- 0.5 mg), FCE 23,884 monotherapy did not affect parkinsonian severity. On the other hand, coadministration of FCE 23,884 with a mildly dyskinetic dose of levodopa, infused intravenously under steady-state conditions, reduced the antiparkinson response by 54 +/- 19% and tended to diminish dyskinesia severity. The results thus fail to suggest any useful role for FCE 23,884 in the symptomatic treatment of PD. Although D2 receptor blockade provided by FCE 23,884 antagonizes both the antiparkinson and dyskinesigenic responses to levodopa, the degree of D1 receptor stimulation appears insufficient to ameliorate parkinsonian symptomatology.
DOI: 10.1002/mds.870110307
PubMed: 8723141
Affiliations:
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pubmed:8723141Le document en format XML
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De Jong</name></author><author><name sortKey="Mouradian, M M" sort="Mouradian, M M" uniqKey="Mouradian M" first="M M" last="Mouradian">M M Mouradian</name></author><author><name sortKey="Chase, T N" sort="Chase, T N" uniqKey="Chase T" first="T N" last="Chase">T N Chase</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1996">1996</date><idno type="RBID">pubmed:8723141</idno><idno type="pmid">8723141</idno><idno type="doi">10.1002/mds.870110307</idno><idno type="wicri:Area/PubMed/Corpus">004842</idno><idno type="wicri:Area/PubMed/Curation">004842</idno><idno type="wicri:Area/PubMed/Checkpoint">004834</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Effect of the putative dopamine D1 agonist and D2 antagonist FCE 23884 on Parkinson's disease.</title><author><name sortKey="Metman, L V" sort="Metman, L V" uniqKey="Metman L" first="L V" last="Metman">L V Metman</name><affiliation wicri:level="1"><nlm:affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892</wicri:regionArea><wicri:noRegion>Maryland 20892</wicri:noRegion></affiliation></author><author><name sortKey="Blanchet, P J" sort="Blanchet, P J" uniqKey="Blanchet P" first="P J" last="Blanchet">P J Blanchet</name></author><author><name sortKey="De Jong, D" sort="De Jong, D" uniqKey="De Jong D" first="D" last="De Jong">D. De Jong</name></author><author><name sortKey="Mouradian, M M" sort="Mouradian, M M" uniqKey="Mouradian M" first="M M" last="Mouradian">M M Mouradian</name></author><author><name sortKey="Chase, T N" sort="Chase, T N" uniqKey="Chase T" first="T N" last="Chase">T N Chase</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="1996" type="published">1996</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 (therapeutic use)</term><term>Carbidopa (adverse effects)</term><term>Carbidopa (therapeutic use)</term><term>Dopamine Agonists (administration & dosage)</term><term>Dopamine Agonists (therapeutic use)</term><term>Dopamine Antagonists (adverse effects)</term><term>Dopamine Antagonists (therapeutic use)</term><term>Dopamine D2 Receptor Antagonists</term><term>Double-Blind Method</term><term>Drug Therapy, Combination</term><term>Ergolines (adverse effects)</term><term>Ergolines (therapeutic use)</term><term>Female</term><term>Humans</term><term>Levodopa (adverse effects)</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Middle Aged</term><term>Neurologic Examination (drug effects)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (physiopathology)</term><term>Receptors, Dopamine D1 (drug effects)</term><term>Receptors, Dopamine D1 (physiology)</term><term>Receptors, Dopamine D2 (physiology)</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Dopamine Agonists</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Dopamine Antagonists</term><term>Ergolines</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Dopamine D1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Receptors, Dopamine D1</term><term>Receptors, Dopamine D2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Dopamine Agonists</term><term>Dopamine Antagonists</term><term>Ergolines</term><term>Levodopa</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" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Dopamine D2 Receptor Antagonists</term><term>Double-Blind Method</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The ergoline derivative FCE 23,884 acts as a dopamine D1 agonist in untreated parkinsonian animals and as a D2 antagonist in animals whose dopamine system is intact or levodopa treated. To evaluate whether this dual action might benefit patients with Parkinson's disease (PD) who have developed levodopa-induced dyskinesias, the motor effects of FCE 23,884 were examined in seven such individuals using a double-blind, placebo-controlled design. At doses up to the maximum tolerated dose (3.5 +/- 0.5 mg), FCE 23,884 monotherapy did not affect parkinsonian severity. On the other hand, coadministration of FCE 23,884 with a mildly dyskinetic dose of levodopa, infused intravenously under steady-state conditions, reduced the antiparkinson response by 54 +/- 19% and tended to diminish dyskinesia severity. The results thus fail to suggest any useful role for FCE 23,884 in the symptomatic treatment of PD. Although D2 receptor blockade provided by FCE 23,884 antagonizes both the antiparkinson and dyskinesigenic responses to levodopa, the degree of D1 receptor stimulation appears insufficient to ameliorate parkinsonian symptomatology.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">8723141</PMID><DateCreated><Year>1996</Year><Month>11</Month><Day>07</Day></DateCreated><DateCompleted><Year>1996</Year><Month>11</Month><Day>07</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>11</Volume><Issue>3</Issue><PubDate><Year>1996</Year><Month>May</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. 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On the other hand, coadministration of FCE 23,884 with a mildly dyskinetic dose of levodopa, infused intravenously under steady-state conditions, reduced the antiparkinson response by 54 +/- 19% and tended to diminish dyskinesia severity. The results thus fail to suggest any useful role for FCE 23,884 in the symptomatic treatment of PD. 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IdType="doi">10.1002/mds.870110307</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Blanchet, P J" sort="Blanchet, P J" uniqKey="Blanchet P" first="P J" last="Blanchet">P J Blanchet</name><name sortKey="Chase, T N" sort="Chase, T N" uniqKey="Chase T" first="T N" last="Chase">T N Chase</name><name sortKey="De Jong, D" sort="De Jong, D" uniqKey="De Jong D" first="D" last="De Jong">D. De Jong</name><name sortKey="Mouradian, M M" sort="Mouradian, M M" uniqKey="Mouradian M" first="M M" last="Mouradian">M M Mouradian</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Metman, L V" sort="Metman, L V" uniqKey="Metman L" first="L V" last="Metman">L V Metman</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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