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Research ArticleArticle

Effects of Pramipexole on Contraversive Rotation and Functional Motor Impairments in 1-Methyl-4-phenyl1,2,3,6-tetrahydropyridine-Induced Chronic Hemiparkinsonian Monkeys

Edward F. Domino, Lisong Ni, Huilei Zhang, Yasuko Kohno and Masashi Sasa
Journal of Pharmacology and Experimental Therapeutics December 1998, 287 (3) 983-987;
Edward F. Domino
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Lisong Ni
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Huilei Zhang
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Yasuko Kohno
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Masashi Sasa
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Abstract

Rotational and functional motor behavioral changes were studied in five MPTP lesioned chronic hemiparkinsonian Macaca nemestrinamonkeys after i.m. pramipexole, a predominant D2 subfamily agonist. Pramipexole induced contraversive rotations in a dose-dependent manner with an optimal dose of 56 μg/kg for ∼2 to 4 hr after injection. Three different rating scales were used to determine drug-induced functional improvement. They included a monkey parkinsonism rating scale, volitional responses to fruit presentations, and number of hand movements that appeared volitional. A dose of 56 μg/kg of pramipexole produced functional improvements on hand disability, and on a parkinsonian rating scale for monkeys in a dose-dependent manner from 32 to 100 μg/kg. These doses produced an increase in significant hand movements in the affected (contralateral) as well as in the normal (ipsilateral) hand to the side of the brain lesion compared with 5% dextrose in water vehicle control. With a dose of 100 μg/kg, the therapeutic effects of pramipexole on hand movements were less than with 56 μg/kg, due to side effects such as scratching.

Footnotes

  • Send reprint requests to: Dr. E. F. Domino, Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109-0632.

  • ↵1 This work was supported by the Psychopharmacology Research Fund 361024.

  • Abbreviations:
    D5W
    5% dextrose in sterile water
    D1-like
    dopamine D1 receptor family
    D2-like
    dopamine D2 family
    5-HT3
    5-hyroxy tryptamine receptor subtype 3
    MPTP
    1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
    Pramipexole
    (S)-2-amino-4,5,6,7-tetrahydro-6-propylamino-benzothiazole, dihydrochloride monohydrate, SND 919 CL2Y
    • Received May 8, 1998.
    • Accepted July 16, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 287, Issue 3
1 Dec 1998
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Research ArticleArticle

Effects of Pramipexole on Contraversive Rotation and Functional Motor Impairments in 1-Methyl-4-phenyl1,2,3,6-tetrahydropyridine-Induced Chronic Hemiparkinsonian Monkeys

Edward F. Domino, Lisong Ni, Huilei Zhang, Yasuko Kohno and Masashi Sasa
Journal of Pharmacology and Experimental Therapeutics December 1, 1998, 287 (3) 983-987;

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Research ArticleArticle

Effects of Pramipexole on Contraversive Rotation and Functional Motor Impairments in 1-Methyl-4-phenyl1,2,3,6-tetrahydropyridine-Induced Chronic Hemiparkinsonian Monkeys

Edward F. Domino, Lisong Ni, Huilei Zhang, Yasuko Kohno and Masashi Sasa
Journal of Pharmacology and Experimental Therapeutics December 1, 1998, 287 (3) 983-987;
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