• Environmental Analysis Health and Toxicology
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• 제21권4호
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• pp.349-355
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• 2006

Dextromethorphan hydrobromide (DXM) has been widely used as a nonopioid antitussive drug with low toxicity and low potential for drug dependency. DXM is a psychotropic drug since 2003 in our country. This study was performed to investigate the immunotoxicity induced by abuse of DXM. Mice were orally exposed to DXM dissolved in saline as concentration of 30, 60, and 120 mg/kg b.w. before (day-2) or after (day+2) immunization (OVA-antigen, day 0). Thereafter, we measured the increased rate of body weight, relative weight of organ (thymus, spleen, liver, kidney) and OVA-specific IgM level in sera. In addition, mouse splenocytes were exposed to various concentration of DXM $(0.001{\sim}100{\mu}M)$ and cultured with B cell mitogen (LPS) and splenocytes proliferations (SP) were measured by MTT-assay. Thymus-weight were slightly changed on day 9 after administration of DXM, but body-, spleen-, liver-, and kidney-weight were not different between control group and DXM-treated group. SP to LPS were significantly decreased at high concentration $(100{\mu}M)$ when compared with controls. When DXM was administered before or after immunization with OVA-antigen, OVA-specific IgM levels were significantly lowered in a dose-dependent manner. These results indicate that DXM nay depress the primary humoral immune response to the initial antigenic challenge.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2004년도 Annual Meeting of the Korean Society ofApplied Pharmacology
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• pp.35-41
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• 2004

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.394.3-395
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• 2002

Dextromethorphan (Romilar. DEX) is a synthetic analogue of codeine. is not classified as a narcotic and is used only for its antitussive effects in Korea. The daily intake by adults range up to 120mg. Usually in the case of traffic accident. alcohol concentration of blood is analyzed in Korea. but drug tests (medicine, narcotic. alcohol) are submitted in Australia. In crimes of violence (2 examples), a traffic and a murder accident. drug testing in urine and blood was performed. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.279.2-280
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• 2003

A simple and accurate reverse-phase high performance liquid chromatography (HPLC) coupled with photodiode array was developed for the determination of dextromethorphan(DM) and its metabolite dextrorphan(DX) in human urine. Chromatographic separation was accomplished on a cyano analytical column at 220 nm using a mobile phase containing 25 mM triethylammonium phosphate buffer(PH 3.0) in a 0-70％ ACN gradient and triazolam(TZ) was used as internal standard(I.S). (omitted)

• Archives of Pharmacal Research
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• 제21권3호
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• pp.286-290
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• 1998

The abuse of zipeprol, an antitussive agent, was found to be most prevalent among young people in Korea. Because abusers take large doses of this drug for its hallucinogenic effects, fatalities from zipeprol overdose abuse have been on the rise since 1991. Since 1991, a total of 69 zipeprol-related deaths have occurred throughout the nation. A demographic study shows that in ninety six percent of cases involving zipeprol alone, the victims were in their teens and twenties. The mate/female ratio in zipeprol related death was 3.5:1. Most of these zipeprol-associated deaths occurred in the larger cities of Seoul and Inchon. The blood concentration of zipeprol ranged from 0.8 to $38.3{\mu}g/mL $in single drug involved deaths, while zipeprol varied from to 35.3 $0.1{\mu}g/mL $in zipeprol and dextromethorphan victims.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.119.1-119.1
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• 2003

To determinate dextromethorphan (DMP) and its active metabolite dextrorphan (DRP) in urine was performed using $REMEDi^TM$ (Rapid EMErgency Drug identification) that is a fully automated multicolumn high performance liquid chromatographic (HPLC) system with a scanning ultraviolet detector. The limits of detection for DMP and DRP were 0.10 and 0.15 $\mu$g/mL, respectively. The standard curves were linear, with correlation coefficients (r ＞ 0.975) in the concentration range of 0.5~10.0 $\mu$g/mL. (omitted)

• Translational and Clinical Pharmacology
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• 제25권3호
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• pp.147-152
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• 2017

This study focused on the role of cytochrome P450 2D6 (CYP2D6) genotypes to predict phenotypes in the metabolism of dextromethorphan. CYP2D6 genotypes and metabolic ratios (MRs) of dextromethorphan were determined in 201 Koreans. Unsupervised clustering algorithms, hierarchical and k-means clustering analysis, and color visualizations of CYP2D6 activity were performed on a subset of 130 subjects. A total of 23 different genotypes were identified, five of which were observed in one subject. Phenotype classifications were based on the means, medians, and standard deviations of the log MR values for each genotype. Color visualization was used to display the mean and median of each genotype as different color intensities. Cutoff values were determined using receiver operating characteristic curves from the k-means analysis, and the data were validated in the remaining subset of 71 subjects. Using the two highest silhouette values, the selected numbers of clusters were three (the best) and four. The findings from the two clustering algorithms were similar to those of other studies, classifying $^*5/^*5$ as a lowest activity group and genotypes containing duplicated alleles (i.e., $CYP2D6^*1/^*2N$) as a highest activity group. The validation of the k-means clustering results with data from the 71 subjects revealed relatively high concordance rates: 92.8% and 73.9% in three and four clusters, respectively. Additionally, color visualization allowed for rapid interpretation of results. Although the clustering approach to predict CYP2D6 phenotype from CYP2D6 genotype is not fully complete, it provides general information about the genotype to phenotype relationship, including rare genotypes with only one subject.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.130.2-131
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• 2000

• Archives of Pharmacal Research
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• 제22권2호
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• pp.113-118
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• 1999

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic $5-HT_{2}$ receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompeti-tive (MI-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsyaptic $5-HT_{2}$receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin $5-HT_{2}$receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the poststynaptic $5-HT_{2}$ receptors.

• 약학회지
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• 제39권4호
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• pp.444-449
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• 1995

Primary cultures of rat cortical and chicken embryonic brain cells were employed to establish a reliable screening method for natural products blocldng or enhancing glutamate-induced neurotoxicity. Exposure of primary cultured rat cortical cells or chicken embryonic brain cells to high dose of glutamate resulted in the fragmentation of neutites and consequent neuronal death. The level of cytoplasmic lactate dehydrogenase(LDH), indicator for cell survival in cultures, was significantly reduced at exposure to glutamate. For the practical application of the methods, series of concentrations of plants extracts and positive control were applied prior to the glutamate insult on primary cultures of rat cortical and chicken embryonic, brain cells. Relative LDH level in cells was measured for the estimation of the effect of the test materials on the glutamatergic neurons. The validity of the present screening method for natural products acting on glutamatergic neurons was examined with dextromethorphan, a known glutamatergic antagonist. The treatment of 100 $\mu{M}$ dextromethorphan prevented the reduction of LDH in rat cortical and chicken embryonic brain cells caused by glutamate insult keeping 60% and 90% of LDH level in normal control, respectively. Above results indicate that primary cultures of rat cortical and chicken embryonic brain cells could be proper systems for the screening of potential natural agents acting on glutamatergic, neurons. Between the two types of cultures, primary culture of chicken embryonic brain cells seemed to be a better system for the primary screening, since it is technically easier and economical compared to that of rat cortical cells.