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 : 006271 ( Main/Exploration ); précédent : 006270; suivant : 006272Sustained‐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 : Cedarbaum [États-Unis] ; Mary Clark [États-Unis] ; Linda H. Toy [États-Unis] ; Alison Green-Parsons [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 1990.
Descripteurs français
- Wicri :
- topic : Thérapeutique.
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), Parkinson's disease, Receptors, Dopamine (drug effects), Receptors, Dopamine D2, Response fluctuation, Therapeutics.
- 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 downregulation of postsynaptic dopamine receptors.
Url:
DOI: 10.1002/mds.870050407
Affiliations:
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Le document en format XML
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<series><title level="j">Movement Disorders</title>
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<term>Antiparkinson Agents</term>
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<term>Carbidopa (administration & dosage)</term>
<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>Parkinson's disease</term>
<term>Receptors, Dopamine (drug effects)</term>
<term>Receptors, Dopamine D2</term>
<term>Response fluctuation</term>
<term>Therapeutics</term>
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<term>Levodopa</term>
<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>
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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 downregulation of postsynaptic dopamine receptors.</div>
</front>
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<region><li>État de New York</li>
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<name sortKey="Clark, Mary" sort="Clark, Mary" uniqKey="Clark M" first="Mary" last="Clark">Mary Clark</name>
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<name sortKey="Toy, Linda H" sort="Toy, Linda H" uniqKey="Toy L" first="Linda H." last="Toy">Linda H. Toy</name>
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