• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.78-78
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• 1993

1) 측좌핵파괴 후 muricide를 비롯하여 startle, struggle등의 정동행동의 변화가 뇌손상 초기에는 현저히 발현되나 muricide를 제외하고 기간경과와 함께 점차 감소한다. 2) 봉선핵파괴 동물은 muricide, moose-eating behavior 등의 극심한 정동행동의 변화를 유발한다. 3) 측자핵파괴로 유발된 muricide는 1-DOPA, nomifensine, desipramine 등에 의하여 현저히 억제되었으나 HPD 에는 감수성이 낮았다. 봉선핵파괴로 유발된 muricide는 L-5-HTP, 4) 봉선핵파괴로 유발된 muricide는 L-5-HTP, clomipramine, nomifensine 등에 의하여 현저하게 억제되었다.

• Progress in Medical Physics
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• v.19 no.2
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• pp.95-101
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• 2008

In this study, we observed the alteration of choline signal intensity in hippocampus region of the depressive rat model induced by forced swimming test (FST). The purpose of this study was to evaluate the antidepressant efficacy in the depressive animal model using MR spectroscopy. Fourteen experimentally naive male Sprague-Dawley rats weighting $160{\sim}180\;g$ were used as subjects. Drug injection group was exposed to the FST except for control group. The drugs were administered subcutaneously (SC) in a volume equivalent to 2ml/kg. And three injections were administered 23, 5, and 1h before beginning the given test. 1H MR spectra were obtained with use of a point resolved spectroscopy (PRESS) localization sequence performed according to the following parameters: repetition time, 2500 ms; echo time, 144 ms; 512 average; 2048 complex data points; voxel dimensions, $1.5{\times}2.5{\times}2.5\;mm^3$ ; acquisition time, 25min. There were no differences in NAA/Cr and Cho/Cr ratio between the right and the left hippocampus both normal control rats and antidepressant-injected rats. Also, no differences were observed in NAA/Cr and Cho/Cr ratio between the normal control rats and the antidepressant-injected rats both the right and the left hippocampus. In this study, we found the recovery of choline signals in the depressive animal model similar to normal control groups as injecting desipramine-HCl which was antidepressant causing anti-immobility effects. Thus, we demonstrated that MR spectroscopy was able to aid in evaluating the antidepressant effect of desipramine-HCl.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.38-38
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• 1992

횐쥐 적출 완류부신을 이용하여 neuronal nicotinic(NN) agonist인 DMPP와 M1-muscarinic agonist인 McN-A-343의 카테콜아민(CA) 분비 작용의 차이와 특성에 대해서 연구한 결과는 다음과 같다. DMPP (100 $\mu$M)와 McN-A-343(100 $\mu$M)은 부신정맥내로 투여시 유의한 카테콜아민 분비작용을 나타내었다. Mol농도로 비교시 McN-A-343의 CA분비작용은 DMPP의 약 1/5정도였다. DMPP의 CA분비작용은 chlorisondamine이나 desipramine 또는 $Ca_2$$^{2}$-free Krebs ＋ EGTA 관류등의 전처치로 의의있게 억제되었으나, pirenzepine, ouabain 및 physostigmine등 전처치에 의해서는 영향을 받지않았다. 그러나 atropine 전처치시 DMPP의 분비작용은 오히려 증강되었다.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.195-195
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• 2001

The inhibitory potentials of TCAs (imipramine, desipramine, amitriptyline, and nortriptyline) on phenytoin p-hydroxylation and probe metabolic pathways of each CYP isoforms were evaluated from incubation studies of human liver microsomes and cDNA-expressed cytochrome P450s in vitro in order to understand the mechanism of drug interaction between TCAs and phenytoin, a substrate of CYP2C9 and CYP2C19. (omitted)

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.95-100
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• 1987

The effects of various drugs on muricide and hyperirritability induced by bilateral lesions of the nucleus accumbens septi (NAB) were investigated in comparison with those on aggression induced by midbrain raphe nuclei-lesioned rats (raphe) and olfactory bulbectomized rats (OB). Muricide in NAB, raphe and OB rats were markedly suppressed by atropine. Muricide in NAB and raphe rats were significantly suppressed by L-DOPA, L-5-HTP, but muricide in OB rats was scarcely suppressed by L-DOPA and L-5-HTP. Hyperirritability in NAB, raphe and OB rats were significantly reduced by L-DOPA and haloperidol but not suppressed by atropine. On the other hand, muricide in NAB rats was markedly suppressed by antidepressants, particularily, nomifensine, clomipramine and desipramine. Muricide in raphe rats was markedly inhibited by nomifensine and clomipramine but only slightly inhibited by desipramine. Muricide in OB rats was markedly suppressed by imipramine. Hyperirritability in NAB, raphe and OB rats were slightly suppressed by antidepressants. These results suggested that the pharmacological characteristics of aggression induced by NAB rats resembles that induced by raphe rats, but differs from that induced by OB rats. It is also suggested that employment of different types of experimentally induced muricide in rats can be useful for the evaluation of antidepressants.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.90-98
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• 1985

1) In the study of the forced-swimming test in mice (FSM), the duration of immobility posture was dose-dependently shortened by ${\alpha}_2$-agonists, clonidine and guanabenz. BH-T 933 and oxymetazoline also decreased it . Xylazine rather increased the immobility duration at low dose. 2) ${\alpha}_1$-Agonists, cirazoline, amidephrine and methoxamine, however, showed inconsistent effect on the immobility duration (ID). 3) The decrease in ID by clonidine and guanabenz was antagonized by pretreatment with yohimbine, idazoxan and phentolamine (${\alpha}_2$antagonist), but not by prazosin and corynanthine (${\alpha}_1$-antagonist) .4) The ID in the FSM was shortened dose-dependently by d-amphetamine, and it was also antagonized by yohimbine, but not by prazosin. 5) In the mice pretreated with either ${\alpha}$-methyl-p-tyrosine or reserpine, or with combination of both, the decrease in ID was still evoked by clonidine. 6) When the mice were chronically treated with antidepressants (desipramine and imipramine), or with electroconvulsive shock, clonidine still decreased the ID as it did in the control. 7) These results provided the evidences to hypothesize that the change of the ID in the FSM is closely related with the postsynaptie ${\alpha}_2$-adrenoceptor located on the central noradrenergic neuron body. Furthermore, it is assumed that this escape-directed behavior enhanced by ${\alpha}_2$-adrenoceptor agonist may be the result in some analogy with the incentive of drives which are directed toward the self-preservation.

• Biomolecules & Therapeutics
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• v.18 no.3
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• pp.262-270
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• 2010

CD95 receptor is a member of tumor necrosis factor receptor family that mediates apoptosis in many cell types when bound by CD95 ligand or cross-linked by agonistic anti-CD95 antibodies. To determine the role of neutral sphingomyelinase (nSMase) on CD95-mediatd apoptosis, human Jurkat T lymphocytes were exposed to recombinant human CD95 ligand. Treatment with CD95 ligand induced cell death in a concentration and time-dependent manner. CD95-induced cell death was suppressed by inhibitors of SMase such as AY9944 or desipramine. Transfection with human nSMase1 siRNA plasmid into CD95 ligand-treated cells significantly prevented CD95-mediated cell death. CD95-mediated elevation of intracellular ceramide level detected by FACS analysis with anti-ceramide antibody was also decreased by nSMase1 siRNA. Knock-down of nSMase1 expression also blocked cytochrome c release into cytosol and caspase-3 cleavage in CD95-treated cells. Taken together, these results suggest that nSMase1 may play an important role in CD95-mediated apoptotic cell death in Jurkat T cells.

• BMB Reports
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• v.39 no.4
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• pp.383-393
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• 2006

Little is known concerning the mechanisms responsible for the transplacental transfer of thiamine. So, the aim of this work was to characterize the placental uptake of thiamine from the maternal circulation, by determining the characteristics of $^3H$-thiamine uptake by a human trophoblast cell line (BeWo). Uptake of $^3H$-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent and energy-independent; 2) pH-dependent (uptake increased as the extracellular medium pH decreased); 3) $Na^+$-dependent and $Cl^-$-independent; 4) not inhibited by the thiamine structural analogs amprolium, oxythiamine and thiamine pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N-methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by the organic cation serotonin, and by two selective inhibitors of the serotonin plasmalemmal transporter (hSERT), fluoxetine and desipramine. We conclude that $^3H$-thiamine uptake by BeWo cells seems to occur through a process distinct from thiamine transporter-1 (hThTr-1) and thiamine transporter-2 (hThTr-2). Rather, it seems to involve hSERT. Moreover, chronic (48 h) exposure of cells to caffeine ($1\;{\mu}M$) stimulated and chronic exposure to xanthohumol and iso-xanthohumol (1 and $0.1\;{\mu}M$, respectively) inhibited $^3H$-thiamine uptake, these effects being not mediated through modulation of the expression levels of either hThTr-1 or hSERT mRNA.

• Journal of Ginseng Research
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• v.17 no.3
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• pp.187-195
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• 1993

We have examined the functional role of central dopaminergic processes on the behavioral pharmacological effects induced by psychotropics and red ginseng saponins of normal rats and compared with that of brain damaged rats. Desipramine and clomipramine produced, a significant depression of the locomotor activity in normal rats, but in brain damaged rats, they did not have any effect throughout the experimental period of 4 hours. Total saponin (50~200 mg/kg), PT (25~50 mg/kg), PD (25~50 mg/kg), $Rg_1$(12.5~25 mg/kg), $Rb_1$ (12.5~50 mg/kg) did not change, and high concentrations of PT (100 mg/kg), PD (100 mg/kg) and $Rg_1$ (50 mg/kg) showed a significant decrease in the locomotor activity of one hour after administration but total saponin (100 mg/kg), PD (25~50 mg/kg), Rgl (12.5 mg/kg), $Rb_1$ (12.5 mg/kg) markedly increased the locomotor activity of four hour after administration in normal rats. On the other hand, total saponin (50 mg/kg), PT (100 mg/kg) and PD (100 mg/kg) Produced a prominent stimulation of the locomotor activity in brain damaged rats. These results suggest that the inhibition of the locomotor activity induced by antidepressants was not affected by the sensitivity of cerebral DA system, whereas red ginseng saponin showed antifatigue effect and also the stimulation of the locomotor activity induced by red ginseng saponin was mediated by the inhibition of cerebral DA system. These psychotropic action of red ginseng saponins could be responsible for the beneficial effects on conditions of fatigue and decreased alertness.

• YAKHAK HOEJI
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• v.39 no.2
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• pp.161-168
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• 1995

Brain dopamine systems play a central role in the control of movement, hormone release, and many complex behavior. The action of dopamine at its synapse is terminated predominately by high affinity reuptake into presynaptic terminals by dopamine transporter (DAT). The dopamine transporter(DAT) is membrane protein localized to dopamine-containing nerve terminals and closely related with cocaine abuse, Parkinsonism, and schizophrenia. In present study, the recombinant plasmid pRc/CMV-DAT, constructed by subcloning of a cDNA encoding a bovine DAT into eukaryotic expression vector pRc/CMV, was stably transfected into CV-1 cells(monkey kidney cell line). The DAT activities in the cell lines selected by Geneticin$^{R}$ were determined by measuring the uptake of $[^3H]$-dopamine. The transfected cell lines showed 30-50 fold higher activities than untransfected CV-1 cell line, and this result implies that DAT is well expressed and localized in transfected cells. The transfected cells accumulated $[^3H]$-dopamine in a dose-dependent manner with a $K_{m}$ of 991.6nM. Even though high doses of norepinephrine, epinephrine, serotonin, and choline neurotransmitters inhibited the uptake of $[^3H]$-dopamine, DAT in transfected cell line was proven to be much more specific to dopamine. The psychotropic drugs such as GBR12909, CFT, normifensine, clomipramine, desipramine, and imipramine inhibited significantly the dopamine uptake in tissue culture cells stably transfected with DAT cDNA. Radioactive in situ hybridization was done to map the cellular localization of DAT mRNA-containing cells in the adult rat central nervous system. The strong hybridization signals were detected only in the substantia nigra pars compacta and ventral tegmental area. The restricted anatomical localization of DAT mRNA-containing cells confirms the DAT as a presynaptic marker of dopamine-containing cells in the rat brain.