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