Effects of pramipexole on contraversive rotation and functional motor impairments in 1-methyl-4-phenyl1,2,3, 6-tetrahydropyridine-induced chronic hemiparkinsonian monkeys.
Rotational and functional motor behavioral changes were studied in five MPTP lesioned chronic hemiparkinsonian Macaca nemestrina monkeys after i.m. pramipexole, a predominant D2 subfamily agonist. Pramipexole induced contraversive rotations in a dose-dependent manner with an optimal dose of 56 microg/kg for approximately 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 microg/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 microg/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 microg/kg, the therapeutic effects of pramipexole on hand movements were less than with 56 microg/kg, due to side effects such as scratching.
Domino
E F
EF
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.
Ni
L
L
Zhang
H
H
Kohno
Y
Y
Sasa
M
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D052160:Benzothiazoles; D015259:Dopamine Agents; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D008254:Macaca nemestrina; D009043:Motor Activity / Q000187:drug effects*; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000209:etiology; D000077487:Pramipexole; D012399:Rotation; D013239:Stereotyped Behavior / Q000187:drug effects; D013844:Thiazoles / Q000627:therapeutic use*; D014836:Volition
D000978:Antiparkinson Agents; D052160:Benzothiazoles; D015259:Dopamine Agents; D013844:Thiazoles; D000077487:Pramipexole; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine