Sustained-release (+)-PHNO [MK-458 (HPMC)] in the treatment of Parkinson's disease: evidence for tolerance to a selective D2-receptor agonist administered as a long-acting formulation.
Identifieur interne : 002841 ( Ncbi/Checkpoint ); précédent : 002840; suivant : 002842Sustained-release (+)-PHNO [MK-458 (HPMC)] in the treatment of Parkinson's disease: evidence for tolerance to a selective D2-receptor agonist administered as a long-acting formulation.
Auteurs : J M Cedarbaum [États-Unis] ; M. Clark ; L H Toy ; A. Green-ParsonsSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1990.
English descriptors
- KwdEn :
- Activities of Daily Living, Antiparkinson Agents, Brain (drug effects), Carbidopa (administration & dosage), Carbidopa (adverse effects), Delayed-Action Preparations, Dopamine Agents, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Combinations, Humans, Levodopa (administration & dosage), Levodopa (adverse effects), Oxazines (administration & dosage), Oxazines (adverse effects), Parkinson Disease (drug therapy), Receptors, Dopamine (drug effects), Receptors, Dopamine D2.
- MESH :
- chemical , administration & dosage : Carbidopa, Levodopa, Oxazines.
- chemical , adverse effects : Carbidopa, Levodopa, Oxazines.
- chemical , drug effects : Receptors, Dopamine.
- chemical : Antiparkinson Agents, Delayed-Action Preparations, Dopamine Agents, Drug Combinations, Receptors, Dopamine D2.
- drug effects : Brain.
- drug therapy : Parkinson Disease.
- Activities of Daily Living, Dose-Response Relationship, Drug, Drug Administration Schedule, Humans.
Abstract
4-Propyl-9-hydroxynaphthoxazine, or MK-458 (HPMC), a selective, nonergot D2 agonist administered orally twice a day in sustained-release form, was studied as adjunctive therapy with carbidopa-levodopa (Sinemet) in 12 Parkinson's disease patients with motor response fluctuations. The dosage of agonist was gradually increased over 12 weeks to a maximum tolerated level of up to 60 mg/day, and that of Sinemet was reduced concurrently. After 8 weeks, reduction of Sinemet averaged 45.1%, but over the next 4 weeks, despite a continued increase in dosage of the agonist, patients were unable to decrease their Sinemet further, and by 12 weeks mean reduction in Sinemet was only 32%. Only five patients completed the planned 24-week study, mostly due to progressive loss of efficacy. The MK-458 is capable of partially substituting for Sinemet in dosages employed in this study. Reduced sensitivity to the drug can appear over a relatively short time, perhaps as a result of down-regulation of postsynaptic dopamine receptors.
DOI: 10.1002/mds.870050407
PubMed: 1979657
Affiliations:
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pubmed:1979657Le document en format XML
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<author><name sortKey="Cedarbaum, J M" sort="Cedarbaum, J M" uniqKey="Cedarbaum J" first="J M" last="Cedarbaum">J M Cedarbaum</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology and Neuroscience, Cornell University Medical College, White Plains, New York.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
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<wicri:cityArea>Department of Neurology and Neuroscience, Cornell University Medical College, White Plains</wicri:cityArea>
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<author><name sortKey="Clark, M" sort="Clark, M" uniqKey="Clark M" first="M" last="Clark">M. Clark</name>
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<author><name sortKey="Toy, L H" sort="Toy, L H" uniqKey="Toy L" first="L H" last="Toy">L H Toy</name>
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<author><name sortKey="Green Parsons, A" sort="Green Parsons, A" uniqKey="Green Parsons A" first="A" last="Green-Parsons">A. Green-Parsons</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Sustained-release (+)-PHNO [MK-458 (HPMC)] in the treatment of Parkinson's disease: evidence for tolerance to a selective D2-receptor agonist administered as a long-acting formulation.</title>
<author><name sortKey="Cedarbaum, J M" sort="Cedarbaum, J M" uniqKey="Cedarbaum J" first="J M" last="Cedarbaum">J M Cedarbaum</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology and Neuroscience, Cornell University Medical College, White Plains, New York.</nlm:affiliation>
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<author><name sortKey="Clark, M" sort="Clark, M" uniqKey="Clark M" first="M" last="Clark">M. Clark</name>
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<author><name sortKey="Toy, L H" sort="Toy, L H" uniqKey="Toy L" first="L H" last="Toy">L H Toy</name>
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<author><name sortKey="Green Parsons, A" sort="Green Parsons, A" uniqKey="Green Parsons A" first="A" last="Green-Parsons">A. Green-Parsons</name>
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<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
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<term>Carbidopa (adverse effects)</term>
<term>Delayed-Action Preparations</term>
<term>Dopamine Agents</term>
<term>Dose-Response Relationship, Drug</term>
<term>Drug Administration Schedule</term>
<term>Drug Combinations</term>
<term>Humans</term>
<term>Levodopa (administration & dosage)</term>
<term>Levodopa (adverse effects)</term>
<term>Oxazines (administration & dosage)</term>
<term>Oxazines (adverse effects)</term>
<term>Parkinson Disease (drug therapy)</term>
<term>Receptors, Dopamine (drug effects)</term>
<term>Receptors, Dopamine D2</term>
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<term>Oxazines</term>
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<term>Levodopa</term>
<term>Oxazines</term>
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<term>Delayed-Action Preparations</term>
<term>Dopamine Agents</term>
<term>Drug Combinations</term>
<term>Receptors, Dopamine D2</term>
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<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brain</term>
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<front><div type="abstract" xml:lang="en">4-Propyl-9-hydroxynaphthoxazine, or MK-458 (HPMC), a selective, nonergot D2 agonist administered orally twice a day in sustained-release form, was studied as adjunctive therapy with carbidopa-levodopa (Sinemet) in 12 Parkinson's disease patients with motor response fluctuations. The dosage of agonist was gradually increased over 12 weeks to a maximum tolerated level of up to 60 mg/day, and that of Sinemet was reduced concurrently. After 8 weeks, reduction of Sinemet averaged 45.1%, but over the next 4 weeks, despite a continued increase in dosage of the agonist, patients were unable to decrease their Sinemet further, and by 12 weeks mean reduction in Sinemet was only 32%. Only five patients completed the planned 24-week study, mostly due to progressive loss of efficacy. The MK-458 is capable of partially substituting for Sinemet in dosages employed in this study. Reduced sensitivity to the drug can appear over a relatively short time, perhaps as a result of down-regulation of postsynaptic dopamine receptors.</div>
</front>
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<region><li>État de New York</li>
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<tree><noCountry><name sortKey="Clark, M" sort="Clark, M" uniqKey="Clark M" first="M" last="Clark">M. Clark</name>
<name sortKey="Green Parsons, A" sort="Green Parsons, A" uniqKey="Green Parsons A" first="A" last="Green-Parsons">A. Green-Parsons</name>
<name sortKey="Toy, L H" sort="Toy, L H" uniqKey="Toy L" first="L H" last="Toy">L H Toy</name>
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<country name="États-Unis"><region name="État de New York"><name sortKey="Cedarbaum, J M" sort="Cedarbaum, J M" uniqKey="Cedarbaum J" first="J M" last="Cedarbaum">J M Cedarbaum</name>
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