Effect Of Piribedil On D₂ Receptor Of Parkinson's Disease

Objective Parkinson' s disease is a common neurological degenerative disease. Changes of D₂ receptor is of great importance in its mechanism. Stimulation of D₂ receptor is receiving more and more concerns. Piribedil has the merits of having significant effect, little side-effect and easiness of drug dosage control. The study of piribedil on literature fastened mostly on clinic aspects. In this article we will investigate the changes of D₂ receptor after the introduction of piribedil from the level of protein and mRNA and so can we provide objective basis for the clinical use of piribedil. At the same time, we will evaluate the clinical value of piribedil. Methods1. 6 patients of Parkinson' s disease without therapy, 4 patients after piribedil therapy, with mean age (66.6 ± 7.1988) years old and mean disease duration(2.6 ± 1.3292) years, took part in the test. 4 volunteers, mean age (69. 75±2. 63) years old, also took part in the test. All of them underwent [(11)^C]-RAC-PET examination, with ten serial 1-minute, ten 2-minute, and thereafter six 3. 33-minute time frames over 50 minutes, providing a total of 26 time frames. After reconstruction, 16-26 frames were selected to calculate the bindings.The [UC]-RAC uptake index was defined as a striatum: cerebellum uptake ratio.2. 60 male C57BL/6J mice with mean weight 20g and mean age 10 weeks old were divided into 3 groups: comparison group, group of injected of MPTP(30 mg / kg) for 3 days and for 7 days. Each group was then divided into piribedil group and no piribedil group respectively. The piribedil group was feed with piribedil 30mg / (Kg ? d). All mice were killed 3 weeks later and ratio of D2R mRNA positive cell in striat area was calculated after in situ hybridization.3. 50 patients of Parkinson' s disease (24 male, 26 female), with mean age of 67.66+10.06 years old and mean disease duration of 4. 86±4.54 years were evaluated with UPDRS table before and after piribedil therapy for 12 weeks and the difference was compared. Piribedil was taken alone or as alignment to other drugs, 50mg/day.Results1. In those patients who received no therapy, the [UC]-RAC binding index in the head of caudate nucleus and putamine nucleus controlateral to the suffered limb is 2. 94> 3. 34 and 3. 27 respectively, which is higher than that of the control group (2. 54, 2. 89 and 2. 72). These two groups of character have statistical difference (p value being 0.046, 0.013 and 0.022), indicating that D2R has increased in number, namely upregulation. In those patients who received piribedil, the [UC]-RAC binding index in the head of caudate nucleus and putamine nucleus controlateral to the suffered limb is 2. 59s 2. 83 and 2. 79 respectively, which is not higher than that of the control group (p value being 0.396,0.276 and 0.2 respectively), indicating that piribedil can reverse the upregulation of D2R.2. The positive ratio of D2R mRNA in the group of 3-day-MPTP-no-therapyis 14. 44%, higher than that of O-day-MPTP-no-therapy group (10. 33%), p value being 0. Oil. In the group of 3-day-MPTP-piribedil, the positive ratio is 11. 31%, much lower than that of 3-day-MPTP -no-therapy group, indicating that piribedil can reverse the increase of D2R mRNA. In groups of 7-day-MPTP, the positive ratio is 9.08% and 9.68% respectively, which is lower than that of 0-day-MPTP groups, but having no statistic difference.3. After piribedil therapy, the symptom of Parkinson' s disease alleviated with 35 patients of distinctive effect, accordingly the ratio being 72.9%. The UPDRS ratio of improved value is 29. 1%, while that of II table, III table, tremor and rigidity being 24. 9%, 19. 9%, 24.9% and 32.9% respectively. All those value before and after piribedil therapy has statistic difference.In those eight newly diagnosed patients, the symptoms of six patients have improved effectively. The effective ratio of UPDRS is 23.4%, while that of II table, III table, tremor and rigidity being 25%, 19. 29%, 11. 5% and 31. 1% respectively. After therapy, the general value of UPDRS has statistic difference. Both the symptoms of rigidity and tremor have improved, but the value of tremor has no statistic difference.In those ten terminally illed patients, the symptoms of six patients have improved effectively. The effective ratio of UPDRS is 41. 9%, while that of II table, III table, tremor and rigidity being 55.4%, 33.9%, 57. 1% and 40. 9% respectively. After therapy, the general value of UPDRS has statistic difference, but which of both rigidity and tremor have no statistic difference.In those 30 mild patients, the symptoms of 23 patients have improved effectively. The effective ratio of UPDRS is 40%, while that of II table,...