Vol. 287, Issue 3, 983-987, December 1998

Effects of Pramipexole on Contraversive Rotation and Functional Motor Impairments in 1-Methyl-4-phenyl1,2,3,6-tetrahydropyridine-Induced Chronic Hemiparkinsonian Monkeys¹

Edward F. Domino, Lisong Ni, Huilei Zhang, Yasuko Kohno and Masashi Sasa

Department of Pharmacology (E.F.D, L.N., H.Z.), University of Michigan, Ann Arbor, Michigan; Product Management Department (Y.K.), Marketing Division, Nippon Boehringer Ingelheim, Hyogo, Japan; and Department of Pharmacology (M.S.), Hiroshima University School of Medicine, Hiroshima, Japan

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 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.