quinagolide and Parkinson-Disease

CV 205-502 (CV) is a long-acting dopamine agonist with potent D2 and weak D1 activity, which has not as yet been tested in patients with Parkinson's disease. We performed a dosage ranging and placebo crossover study in six patients to evaluate the efficacy and tolerance of CV when used as an adjunct to Sinemet in patients with Parkinson's disease. All patients had striking improvement. This effect was lost with placebo substitution and regained with reintroduction of CV. Benefits were sustained throughout the 6 month study. Single daily dosing could sustain the response in all but one patient. Adverse effects were mild and transient and resolved with dosage manipulation or a divided dosage regimen. CV is a promising drug for use in Parkinson's disease and further studies are indicated to test its long-term safety and efficacy.

Topics: Adult; Aged; Aminoquinolines; Antiparkinson Agents; Carbidopa; Dopamine Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease

The distribution and density of dopamine D1 and D2 receptors were examined by autoradiography in postmortem brain tissue from patients with pathological diagnosis of Parkinson's disease, status lacunaris, clinical parkinsonism without neuropathological lesions and in age-matched controls. The D1 antagonist [3H]SCH 23390 and the D2 agonist [3H]CV 205-502 were used as ligands. No significant differences in the distribution or density of D1 or D2 receptors were found in Parkinson's disease in the areas examined, including the nucleus caudatus, putamen, globus pallidus and substantia nigra. In contrast, cases presenting lacunar lesions in the striatum showed marked decreases in D1 and D2 receptor densities in this region. Patients clinically diagnosed as parkinsonians but without Parkinson's disease lesions or striatal lacunar softenings showed reduced densities of D2 receptors in the nucleus caudatus and putamen, while in the substantia nigra the densities were comparable to controls. In the basal ganglia of these cases D1 receptors were slightly decreased.

Topics: Aged; Aged, 80 and over; Aminoquinolines; Autoradiography; Benzazepines; Brain; Female; Humans; Male; Middle Aged; Parkinson Disease; Receptors, Dopamine; Syndrome