Volume 5, Issue 4 p. 298-303
Article

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

Dr. Jesse M. Cedarbaum

Corresponding Author

Dr. Jesse M. Cedarbaum

Parkinson and Movement Disorders Clinic, Department of Neurology and Neuroscience, Cornell University Medical College, the Burke Rehabilitation Center, White Plains, and the New York Hospital, New York, New York, U.S.A.

Suite 10, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, U.S.A.Search for more papers by this author
Mary Clark

Mary Clark

Parkinson and Movement Disorders Clinic, Department of Neurology and Neuroscience, Cornell University Medical College, the Burke Rehabilitation Center, White Plains, and the New York Hospital, New York, New York, U.S.A.

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Linda H. Toy

Linda H. Toy

Parkinson and Movement Disorders Clinic, Department of Neurology and Neuroscience, Cornell University Medical College, the Burke Rehabilitation Center, White Plains, and the New York Hospital, New York, New York, U.S.A.

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Alison Green-Parsons

Alison Green-Parsons

Parkinson and Movement Disorders Clinic, Department of Neurology and Neuroscience, Cornell University Medical College, the Burke Rehabilitation Center, White Plains, and the New York Hospital, New York, New York, U.S.A.

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First published: 1990
Citations: 12

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.