• The Korean Journal of Physiology and Pharmacology
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• 제13권2호
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• pp.71-78
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• 2009

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-$HT_{2A}$, Ki=0.61 nM, 5-$HT_{2C}$, Ki=20.7 nM) and dopamine ($D_2$, Ki=45.9 nM, $D_3$, Ki=42.1 nM) receptors with over $10\sim100$-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing ($ED_{50}$=0.93 mg/kg) and DOI-induced head twitch ($ED_{50}$=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine ($ED_{50}$=0.54 mg/kg) and the avoidance response ($ED_{50}$=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose ($ED_{50}$=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.350-356
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• 2015

Functional dyspepsia (FD) is a prevalent idiopathic upper gastrointestinal (GI) disorder characterized by diverse symptomatology including epigastric pain or discomfort, postprandial fullness, and early satiety. Although its pathophysiological mechanisms have not yet been fully established, the available studies suggest that the etiology of FD is invariably multifactorial. Benachio-F$^{(R)}$ (BF) is a proprietary liquid formulation of 7 herbal extracts that has been proposed to address this multifactorial etiology using multi-drug phytotherapy. The pharmacological effects of BF, in comparison with those of two other herbal products (Whalmyungsu$^{(R)}$; WM and Iberogast$^{(R)}$; IB) were evaluated in rats. In a laparotomy-induced rat model of delayed GI transit, BF significantly accelerated the delayed gastric emptying caused by morphine, apomorphine, and cisplatin, and also significantly increased mean gastric transit, as compared to the control animals. BF markedly increased gastric accommodation in rats and produced higher gastric volume values than did the control treatment. The effects of BF were generally comparable or superior to those of WM and IB in these models. Furthermore, BF significantly stimulated biliary flow, as compared to the control treatment. These results indicated that BF might have great potential as an effective phytotherapeutic agent capable of reducing GI symptoms and increasing quality of life in FD patients.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.511-521
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• 2002

The purpose of this study was to determine whether bromocriptine affects the catecholamines (CA) secretion evoked in isolated perfused rat adrenal glands, by cholinergic stimulation, membrane depolarization and calcium mobilization, and to establish the mechanism of its action. The perfusion of bromocriptine ($1~10{\;}{\mu}M$) into an adrenal vein, for 60 min, produced relatively dose-dependent inhibition in the secretion of catecholamines (CA) evoked by acetylcholine (ACh, 5.32 mM), DMPP ($100{\;}{\mu}M$ for 2 min), McN-A-343 ($100{\;}{\mu}M$ for 2 min), cyclopiazonic acid (CPA, $10{\;}{\mu}M$ for 4 min) and Bay-K-8644 ($10{\;}{\mu}M$ for 4 min). High $K^+$ (56 mM)-evoked CA release was also inhibited, although not in a dose-dependent fashion. Also, in the presence of apomorphine ($100{\;}{\mu}M$), which is also known to be a selective $D_2$-agonist, the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly depressed. However, in adrenal glands preloaded with bromocriptine ($3{\;}{\mu}M$) in the presence of metoclopramide ($15{\;}{\mu}M$), a selective $D_2$-antagonist, the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid considerably recovered as compared to that of bromocriptine only. Taken together, these results suggest that bromocriptine can inhibit the CA secretion evoked by stimulation of cholinergic receptors, as well as by membrane depolarization, in the perfused rat adrenal medulla. It is thought this inhibitory effect of bromocriptine may be mediated by inhibiting the influx of extracellular calcium and the release from intracellular calcium stores, through the activation of dopaminergic $D_2$-receptors located in the rat adrenomedullary chromaffin cells. Furthermore, these findings also suggest that the dopaminergic $D_2$-receptors may play an important role in regulating adrenomedullary CA secretion.

• BMB Reports
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• 제56권3호
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• pp.202-207
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• 2023

We investigated the neuroprotective effects of deca nano-graphene oxide (daNGO) against reactive oxygen species (ROS) and inflammation in the human neuroblastoma cell line SH-SY5Y and in the 6-hydroxydopamine (6-OHDA) induced Parkinsonian rat model. An MTT assay was performed to measure cell viability in vitro in the presence of 6-OHDA and/or daNGO. The intracellular ROS level was quantified using 2',7'-dichlorofluorescein diacetate. daNGO showed neuroprotective effects against 6-OHDA-induced toxicity and also displayed ROS scavenging properties. We then tested the protective effects of daNGO against 6-OHDA induced toxicity in a rat model. Stepping tests showed that the akinesia symptoms were improved in the daNGO group compared to the control group. Moreover, in an apomorphine-induced rotation test, the number of net contralateral rotations was decreased in the daNGO group compared to the control group. By immunofluorescent staining, the animals in the daNGO group had more tyrosine hydroxylase-positive cells than the controls. By anti-Iba1 staining, 6-OHDA induced microglial activation showed a significantly decrease in the daNGO group, indicating that the neuroprotective effects of graphene resulted from anti-inflammation. In conclusion, nano-graphene oxide has neuroprotective effects against the neurotoxin induced by 6-OHDA on dopaminergic neurons.

• 한국발생생물학회지:발생과생식
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• 제15권2호
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• pp.143-150
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• 2011

이 연구는 수중 운동, 균형 훈련과 복합 운동이 파킨슨 유발 흰쥐 모델에 미치는 영향을 관찰하기 위해 수산화도파민(6-hydroxydopamine)을 흰쥐의 좌측 내측전뇌다발에 주사하여 파킨슨 모델을 제작하였다. 실험동물은 수중 운동을 적용한 실험군 I, 균형 훈련을 적용한 실험군 II, 복합 운동(수중 운동+균형 훈련)을 적용한 실험군 III, 수술 후 표준사육장에서 운동을 적용하지 않은 대조군으로 배치하였다. 수술 후 7일, 14일, 21일에 실험동물의 중뇌 흑질의 도파민 세포감소를 관찰하기 위하여 TH(tyrosine hydroxylase)의 발현 양상을 관찰하였고, 행동학적 검사로 수술 후 1일, 7일, 14일,21일에 아포몰핀유도 회전 검사를 실시하였다. 실험 결과, 실험군들에서 대조군에 비하여 유의하게 높은 TH 발현과 아포몰핀유도 회전수를 보였다. 하지만 실험군들 사이에는 유의한 차이가 나타나지 않았다. 이상의 결과에서 파킨슨유발 흰쥐모델이 기능 회복에 수중 운동과 균형 훈련이 효과적임을 알 수 있었으며, 흑질 치밀부의 도파민성 신경섬유의 증감을 나타내는 TH의 발현에도 수중 운동과 균형 훈련이 효과적임을 알 수 있었다.

• Journal of Ginseng Research
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• 제23권2호
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• pp.115-121
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• 1999

에탄올 단기 투여로 유발되는 기억획득의 손상에 대한 홍삼 조 사포닌 성분을 비롯한 수종의 뇌기능개선 후보약물의 급성 및 연속 투여 작용을 검토하였다. 에탄올 급성 투여로 유발된 학습획득 손상 흰쥐에 GABA신경 억제 성 약물인 picrotoxin 급성 투여시 에탄올 투여 흰쥐의 학습획득 손상 작용은 유의성 있는 개선효과를 나타내었으나 diazepam, acetyl-L-carnitine 및 apomoiphie투여 군은 현저한 영향을 미치지 않았다. 급성 홍삼 total saponin 투여군은 에탄올 투여 흰쥐의 학습획득 손상을 유의성 있게 억제하였으며 7일간의 연속 투여에 의해 그 효과가 현저하게 증가하였다. 급성 및 연속 deprenyl투여군은 모두 유의성 있는 억제 작용을 나타내었으나 protopanaxatriol, protopanaxadiol 및 centrophenoxine 투여 군은 모두 현저한 억제작용을 나타내지 않았다. 급성 piracetam 투여 및 연속 N-methyl-D-glucamine투여 군은 유의성 있는 억제효과를 나타내었다. 한편, 에탄올 투여 희쥐의 학습획득 손상에 대한 홍삼 total saponin 연속 투여효과는 ${\alpha}-methyl-전 처치에 의해 유의성 있게 차단되었으나 N-methyl-D-glucamine 연속투여에 의한 억제효과는 부분적으로 차단되었으며, 연속 depreny의 효과는 용량에 따라 차단 또는 증강되는 등 전혀 다른 효과를 나타내었다. 이러한 결과는 에탄올 급성 투여 흰쥐의 학습획득 손상은 picrotoxine, 홍삼 조사포닌, N-methyl-D-glucamme및 deprenyl의 급성 또는 연속 투여가 효과적이며 홍삼 조 사포닌과 N-methyl-D-glucamine 및 deprenyl의 연속 투여 효과는 뇌중 도파민 신경활성에 미치는 영향이 상위함을 나타내고 있다. 따라서 에탄올 급성투여 흰쥐의 학습획득 손상은 일차적으로 뇌중 GABA 신경활성의 억제에 기인하며 이차적으로 도파민신경활성과의 균형의 중요성을 시사하고 있다.