• 약학회지
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• 제36권3호
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• pp.285-290
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• 1992

After rats were exposed to 5,000 ppm carbon monoxide for 30 minutes, the amounts of catecholamine neurotransmitters in stratum were measured using high performance liquid chromatograph equipped with electrochemical detector. The concentration of dopamine in stratum was significantly decreased after carbon monoxide intoxification, but those of dihydroxyphenylacetic acid, norepinephrine, and epinephrine was not changed. However the pretreatments of Ginseng total saponin and panaxatriol saponin increased the concentrations of dopamine and its acidic metabolites (DOPAC and HVA). Ginseng total saponin also increased the concentrations of norepinephrine and epinephrine. Similar results were obtained from aged rats.

• 분석과학
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• 제8권2호
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• pp.215-220
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• 1995

흰쥐 뇌의 선조체로부터 catecholamine, indoleamine 및 대사산물을 동시분석할 수 있는 간편한 방법을 제시하였다. 기기는 ECD를 장착한 HPLC를 사용하였고, 고정상인 $C_{18}$ 컬럼에서, 이 동상은 10mM citric acid, 0.13mM $Na_4EDTA$, 0.58mM SOS를 함유하는 35mM sodium acetate buffer(pH 3.4) : MeOH=85:15가 최적이었다. 이 때 컬럼온도는 $30^{\circ}C$였다. 이 조건으로 dopamine(DA), 3, 4-dihydroxyphenyl acetic acid(DOPAC), homovanilic acid(HVA), 5-hydroxyindole acetic acid(5-HIAA), serotonin(5-HT) 및 noradrenaline(NA)을 미량까지 분석할 수 있었고, 검출한계는 각 성분에 대해 1회 주입당 2~10pg이었다. 이 방법으로 흰쥐의 주령 및 성별에 따른 선조 체내 생체아민과 대사산물의 함량을 비교하였다. 7주령 쥐에서 암컷은 수컷보다 DA와 5-HT의 함량이 유의성 있게 높은 것으로 나타났으며, 주령이 증가함에 따라 암컷에서 DOPAC의 함량이 유의적으로 증가하였다.

• 약학회지
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• 제49권4호
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• pp.355-364
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• 2005

A neurotoxin, 6-hydroxydopamine (6-OHDA) has long been used to form a Parkinson's disease (PD) model by inducing the lesion in catecholaminergic pathways, particularly the nigrostriatal dopamine (DA) pathway. Whereas l-deprenyl, a selective inhibitor of monoamine oxidase (MAO) type B, is now widely used in the treatment of PD, the precise action mechanism of the drug remains elusive. In this study, we investigated whether l-deprenyl shows protective effect against the DA depletion induced by 6-OHDA in rat brain, and against 6-OHDA-induced neurotoxicity and oxidative stress in catecholaminergic neuroblastoma SH-SY5Y cells that are known to lack MAO-B activity. Pretreatment of l-deprenyl significantly enhanced the striatal DA, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and 3-methoxytyramine levels compared to the untreated 6-OHDA-lesioned rat, indicating that l-deprenyl pretreatment prevents 6-OHDA-induced depletion of not only striatal dopamine but also its metabolites. Treatment of 6-OHDA for 24hrs decreased the cell viability and increase the generation of ROS in dose-dependent manners. We further investigated whether caspase activity is involved in the action of l-deprenyl. Treatment of l-deprenyl $(0.1\~100{\mu}M)$ did not produce any changes in 6-OHDA-induced cleavage of poly (ADP-ridose) polymerase in SH-SY5Y cells. Our results suggest that the neuroprotective effect of l-deprenyl against 6-OHDA is due to its increased scavenger activity, but independent of inhibition of MAO-B or caspase-3 activation.

• 약학회지
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• 제43권1호
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• pp.33-41
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• 1999

Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.