• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.2
• /
• pp.71-78
• /
• 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
• /
• v.23 no.4
• /
• pp.350-356
• /
• 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
• /
• v.25 no.4
• /
• pp.511-521
• /
• 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
• /
• v.56 no.3
• /
• pp.202-207
• /
• 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.

• Development and Reproduction
• /
• v.15 no.2
• /
• pp.143-150
• /
• 2011

The objective of this study was to determine the effect of exercise on a hemiparkinsonian rat model. Nigrostriatal dopamine cell lesions were produced by injecting 6-hydroxydopamine at the left medial forebrain bundle of rats. In this study, the rats were divided into the following 4 groups: the control group without any exercise, experimental group I with aqua-exercise (Exp I), experimental group II with balance exercise (Exp II) and experimental group III with complex exercise (aqua-exercise+balance exercise; (Exp III)). Exercises were applied to all the experimental groups after the operation. In order to observe the dopaminergic cell loss, we assessed the level of tyrosine hydroxylase (TH) expression in the midbrain of rats, and performed the apomorphine-induced rotation test at postoperative days (PDs) 7, 14, and 21. Experimental groups had significantly higher TH-immunoreactivity and behavioral performance than the control group. However, there was no difference in TH-immunoreactivity and behavioral performance across the experimental groups. These results suggest that the application of aqua-exercise and balance exercise could suppress dopaminergic cell loss in the substantia nigra of rat brains and could increase behavioral recovery in hemiparkinsonian rats.

• Journal of Ginseng Research
• /
• v.23 no.2 s.54
• /
• pp.115-121
• /
• 1999

Effects of single and repeated administration of various nootropic candidates were examined on impaired acquisition by single oral administration of 3 g/kg ethanol (EtOH) in step through test. The inhibitory effect of EtOH on acquisition was significantly reduced by single picrotoxin, but not affected by diazepam, acetyl-L-carnitine and apomorphine. Single or repeated red ginseng total saponin and deprenyl, single piracetam, repeated N-methyl-D-glucamine, but not single or repeated protopanaxadiol, protopanaxatriol and centrophenoxine significantly ameliorated the impairment of acquisition by EtOH. On the other hand, the inhibitory effect of repeated red ginseng total saponin but not that of repeated N-methyl-D-Glucamine, was significantly blocked by pretreatment of $\alpha$-methyl-$\rho$-tyrosine, a inhibitor of catecholamine synthesis. Whereas, the inhibitory effect of repeated deprenyl on EtOH amnesia was exaggerated by $\alpha$-methyl-$\rho$-tyrosine. These results suggest that the amelioration processes of drugs on ethanol amnesia involve complex mechanism between the central GABAergic and dopaminergic neuronal activity in memory and learning, although the effects of repeated drugs administration are not yet clear.