住吉 周子 東邦大学, 医学部, 助手 (20256738)
NIIZUMA Masamichi TOHO UNIVERSITY,FOURTH DEPARTMENT OF INTERNAL MEDICINE,ASSISTANT, 内科学第4講座, 助手 (70198414)
ARAKI You TOHO UNIVERSITY,FOURTH DEPARTMENT OF INTERNAL MEDICINE,ASSISTANT PROFESSOR, 内科学第4講座, 講師 (80120228)
|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1996 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥700,000 (Direct Cost : ¥700,000)
We have been studied the effects of debrisoquin to the central nervous system. The chemical structure of debrisoquin resembles to tetrahydroisoquinolin that thought to be one of the candidate substances for the cause of Parkinson disease. It is known that cytochrome P-450 IID6 is the metabolizer both debrisoquin and tetrahydroisoquinolin. There are significant differences on debrisoquin metabolisms in each individual. There are some poor metabolizers of debrisoquin, and the onset rate of Parkinson disease who show a low enzyme activity or enzyme defect of cytochrome P-450 IID6 is 2-fold higher than the normal persons. In the present study, we examined changes of monoamine in the rats brain with debrisoquin administration and debrisoquin administered after pretreatment of estradiol by intraperitoneal injection.
[Results] 1. Debrisoquin administration alone : There were no significant effects on dopamine, DOPAC and HVA.Whereas, 5-HT was significant decreased in many parts of the rat brain
, also 5-HIAA was decreased in same parts. 2. Debrisoquin administered after estradiol pretreatment (debrisoquin administered after destroyed blood-brain-barrier) : There were no significant effects on dopamine, DOPAC and HVA between debrisoquin group and debrisoquin administered after estradiol pretreatment group. Whereas, 5-HT was significant increased in almost parts of the brain, and also 5-HIAA was increased in many parts of the brain.
[Discussion] In our previous study, in rodents, selegiline and lazabemide such as MAO-B inhibitor did not show significant change on monoamine in rats brain. Debrisoquin, peripheral MAO-A inhibitor also did not show no significant changes on dopamine in rats brain. Moreover, after destroyed blood-brain-barrier, debrisoquin gave no significant changes on dopamine, DOPAC and HVA.The reasons why debrisoquin gave no significant changes on dopaminergic system are still obscure. Whereas, in the debrisoquin administration alone, decrease of 5-HT was thought to be through the noradrenergic system, on the other hand, in debrisoquin administration after destroyed blood-brain-barrier, 5-HT was increased by debrisoquin as a MAO-A inhibitor.