Edward F. Domino (1), Lisong Ni (1), Huilei Zhang (1), Yasuko Kohno (2)
and Masashi Sasa (3)
(1) Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA
(2) Product Management Department, Marketing Division, Nippon Boehringer Ingelheim, Kawanishi 666-0193, Japan
(3) Department of Pharmacology, Hiroshima University School of Medicine, Hiroshima 734-8551, Japan
Abstract: The effects of talipexole on functional motor improvement in comparison with contraversive circling were studied in five chronic (5 - 7 years post MPTP-lesioned) hemiparkinsonian Macaca nemestrina monkeys. Talipexole induced contraversive rotations in a dose of 32 microg/kg for about 1 hr after i.m. injection. Larger doses (56 and 100 microg/kg, i.m.) produced less effect due to sedation. Three different rating scales were used to assess functional improvement, including a clinical parkinsonism rating scale, volitional responses to fruit presentations, and number of significant hand movements. The optimal dose of talipexole was 32 microg/kg, i.m. Functional improvement by talipexole, including clinical parkinsonian rating scales and significant hand movements, as well as contraversive circling in hemiparkinsonian monkeys, confirm that this chronic animal model is useful in preclinical testing of drugs for the treatment of human parkinsonism.
Keywords: Talipexole, MPTP, Chronic hemiparkinsonism (monkey), Functional improvement, Dopamine D2-like receptor agonist