• Korean Journal of Pharmacognosy
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• v.26 no.4
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• pp.349-354
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• 1995

Crude methanolic(80%) extracts from 109 kinds of traditional herbal drugs were randomly screened for inhibitory effects on 5-hydroxytryptamine(5-HT) uptake in primary cultured rat brainstem neurons. Rat brainstem neurons were cultured from embryonic day 14, and maintained for 7-9 days in vitro. Clomipramine (500 nM), a reference drug, decreased 5-HT uptake to 16% of control values. Of the 109 herbal drugs screened, Citri immaturi Pericarpium(靑皮), Coptidis Rhizoma(黃蓮), Cnidii Rhizoma(土川芎) showed the most potent 5-HT uptake inhibiting activities. These herbal drugs, at the concentration of $10{\;}{\mu}g/ml$, inhibited 5-HT uptake 69, 69, and 57% respectively, when inhibition(%) was expressed as a relative value compared to the 500 nM clomipramine-induced inhibition.

• YAKHAK HOEJI
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• v.51 no.2
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• pp.133-139
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• 2007

A simple and sensitive HPLC-MS method for quantitation of 10${\alpha}$-methoxy-9,10-dihydrolysergol (MDL), the main metabolite of nicergoline, in human plasma was developed and the bioavailability parameters of MDL was assessed in Korean healthy male volunteers. Clomipramine was used as an internal standard. MDL and internal standard in plasma sample were extracted using ethyl acetate. A centrifuged upper layer was then evaporated and reconstituted with mobile phase of 10 mM ammonium acetate-acetonitrile (10 : 90, v/v). The reconstituted samples were injected into a Zorbax SB-C8 column (2.1${\times}$150 mm,5 ${\mu}$m) at a flow-rate of 0.3 ml/min. Using MS with selected ion monitoring (SIM) mode, MDL and clomipramine were detected without severe interference from human plasma matrix. MDL produced a protonated molecular ion ([M+H]$^+$) at m/z 287. Internal standard produced a protonated molecular ion ([M+H]$^+$) at m/z 315. A linear relationship for MDL was found in the range of 2.5${\sim}$100 ng/ml. The lower limit of quantitation (LLOQ) was 2.5 ng/ml with acceptable precision and accuracy. The intra- and inter-day validation for all coefficients of variation (R.S.D.%) were found less than 15%. Main pharmacokinetic parameters of 30 mg of nicergoline were revealed as follows: AUC$_t$ 321.1${\pm}$64.5 ng${\cdot}$hr/ml, C$_{max}$, 51.2${\pm}$25.3 ng/ml, T$_{max}$ 3.6${\pm}$1.5 hr, K$_{el}$ 0.12${\pm}$0.07 hr$^{-1}$ and t$_{1/2}$ 7.6${\pm}$3.4 hr. Inter subject variations and race differences were shown in comparison with the published data in the literature.

• Journal of Veterinary Clinics
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• v.29 no.6
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• pp.494-497
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• 2012

A 6-year-old castrated male Miniature Pinscher dog was referred due to shaking, panting and inappropriate elimination during thunderstorms. The dog had noise phobia after a car accident two years ago. The intensity of the fear of noise, especially with thunderstorms, worsened during the past 3 months (thunderstorm season). Physical examination revealed hyperthermia, tachypnea (panting), mild tachycardia, and an elevated systolic blood pressure. Laboratory examination revealed mild polycythemia with a lower oxygen pressure and saturation. Based on the history, physical examination, and laboratory tests, the dog was diagnosed as a noise phobia concurrent with relative polycythemia. Treatment was initiated with behavior modification with desensitization, counter-conditioning, and medication. Music therapy was also used and appeared to be beneficial. Clinical signs including polycythemia are improved. This case indicates that relative polycythemia can be occurred by chronic mental stress, such as noise phobia in a dog.

• 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.57 no.4
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• pp.289-292
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• 2013

A total of 2,080 forensic autopsies in Seoul, Incheon and Gyeonggi province were performed by the National Forensic Service (NFS) in 2010. After analysing blood samples collected at autopsies by GC-MS and LC-MS/MS, the types and prevalence of drugs and poisons in blood were investigated using our laboratory information management system. Among 2,080 cases, 1,061 cases (51%) were positive for drugs and poisons. Surprisingly, antidepressants were identified in 137 cases which comprised 13% of the positive cases. Twelve different kinds of antidepressants were determined: Amitriptyline, fluoxetine, nortriptyline, trazodone, imipramine, mirtazapine, citalopram, venlafaxin, clomipramine, paroxetine, sertraline and bupropion. Amitriptyline was the most frequently detected antidepressant and was identified in 39 cases. Moreover, amitriptyline, fluoxetine, and nortriptyline were included in the list of the 20 most commonly encountered drugs or poisons in the analysis of blood collected at autopsies from 2007 to 2009, indicating the prevalence of their use. In this study, the 137 antidepressant-related deaths were classified by the mode of death to predict the prevalence of these drugs. As a result, those deaths were divided into four groups based on the cause and mode of death: 56 cases of suicide with fatal concentrations of antidepressant drugs in blood, 6 homicidal cases directly or indirectly related to antidepressants, 59 natural deaths with antidepressants detected in blood and 16 deaths caused by fire or other accidents with antidepressants detected in blood. Because incidents involving antidepressants have been increasing, especially in suicides or homicides, it is necessary for the health authorities and law enforcement administrations to cooperate and share the statistical data for curbing the abuse of antidepressants. This report is expected to provide the reference data related with antidepressants for the investigation of the deaths.

• 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.