• YAKHAK HOEJI
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• v.46 no.3
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• pp.179-184
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• 2002

The abuse of dextromethorphan has been prevalent for 15 years in Korea and its fatal cases were reported even though it has proved to be very safe. In this study, to investigate the safety and tolerance assessment of dextromethorphan, the metabolic phenotyping and genotype of dextromethorphan were studied. After a single 30 mg of dextromethorphan oral administration to 74 volunteers, concentration of dextromethorphan and its metabolites, dextrorphan, hydroxymorphinan and methoxymorphinan were measured in urine which collected during 8hrs after the drug administration. CYP2D6 phenotype was determined from the ratio of dextromethorphan to dextrorphan. GC/MS was used to quantify dextromethorphan and its metabolites. For genotyping, mutant alleles of the CYP2D6 gene were identified. 24 subjects (32.4％) were homozygous for CYP2D6＊10B, 29 subjects (39.2％) were heterozygous for this allele, while in 21 subjects (28.4％) no exon 1 mutation could be found. The frequency of CYP2D6＊10B-allele containing the 188C T mutation was 54％ of total subjects studied.

• Proceedings of the PSK Conference
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• 2003.04a
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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)

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.1-9
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• 1995

The slow development of histopathological changes and long period required for stabilization of lesions have suggested that secondary injury processes exacerbate the effect of initial mechanical insult after traumatic spinal cord injury (SCI). The importance of glutamate receptors in the normal functions of spinal cord, in concert with the large body of evidence that points to their involvement in neurotoxicity due to both ischemic and traumatic insults to the CNS, suggested a probable role of glutamate receptors in secondary injury process after traumatic SCI. In order to investigate the involvement of excitatory amino acid in the secondary injury process after SCI, this study examined the effect of dextrorphan, a noncompetitive NMDA receptor antagonist, on the recovery of hindlimb function and the residual tissue at injury site following SCI. Locomotor function was assessed using open field test (21 point scale). At 8 weeks spinal cord tissue was examined using quantitative histopathologic technique. Prior to surgery female Long-Evans rats were adapted to the test environment. Rats received laminectomies (T9/T10), and spinal cord contusions (NYU impactor) were produced by a 10 gm weight dropped 25 mm. DXT (15 or 30 mg/kg, i.p.) or saline was injected 15 min before contusion. Behavioral testing resumed 2 days post-injury and continued twice a week for 8 weeks. No differences between DXT and saline groups were found for hindlimb function and sparing tissue at the lesion site. These results suggest that NMDA receptor might not be involved in secondary injury processes after traumatic SCI.

• Archives of Pharmacal Research
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• v.22 no.2
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.247-247
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• 1996

Previous work in our laboratory has shown that noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced inhibition of apomorphine-induced cage climbing behavior in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of dopaminergic function at the postsynaptic dopamine (DA) receptors: Therefore, in order to definitively establish the involvement of NMDA receptor in the apomorphine-induced dopaminergic response at the postsynaptic DA receptor, it is necessary to investigate whether or not the noncompetitive NMDA receptor antagonists would inhibit these phenomena not only in intact mice but also in the mice that are devoid of any involvement of indirect dopaminergic function. To minimize the risk of any indirect involvement of NMDA antagonists with DA neurons, vesicular DA stores were first depleted with reserpine.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.102-102
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• 1997

The purpose of this study was to determine the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both the competitive (AP-5 and D-CPP) and the noncompetitive (MK-801, ketamine, dextrorphan and dextromethorphan) N-methyl-D-aspartate (NMDA) receptor antagonists markedly enhanced 5-HT(5-hydroxytryptamine)-induced selective serotonergic behavior, head-twitch response (HTR), in mice. These results suggest that the glutamatergic neurotransmission may modulate serotonergic function at the 5-HT receptor. The precise relationship between glutamatergic and serotonergic system is as yet undefined. However, these are the first data available regarding glutamatergic modulation of serotonergic function at the 5-HT receptor in intact mice, and the present results support the notion that the NMDA receptors may play important roles in the glutamatergic modulation of serotonergic function at the 5-HT receptor.

• Proceedings of the PSK Conference
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• 2003.10b
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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)

• Journal of Ginseng Research
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• v.40 no.4
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• pp.375-381
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• 2016

Background: We evaluated the drug interaction profile of Red Ginseng (RG) with respect to the activities of major cytochrome P450 (CYP) enzymes and the drug transporter P-glycoprotein (P-gp) in healthy Korean volunteers. Methods: This article describes an open-label, crossover study. CYP probe cocktail drugs, caffeine, losartan, dextromethorphan, omeprazole, midazolam, and fexofenadine were administered before and after RG supplementation for 2 wk. Plasma samples were collected, and tolerability was assessed. Pharmacokinetic parameters were calculated, and 90% confidence intervals (CIs) of the geometric mean ratios of the parameters were determined from logarithmically transformed data using analysis of variance after RG administration versus before RG administration. Results: Fourteen healthy male participants were evaluated, none of whom were genetically defined as poor CYP2C9, 2C19, and CYP2D6 metabolizers based on genotyping. Before and after RG administration, the geometric least-square mean metabolic ratio (90% CI) was 0.870 (0.805-0.940) for caffeine to paraxanthine (CYP1A2), 0.871 (0.800-0.947) for losartan (CYP2C9) to EXP3174, 1.027 (0.938-1.123) for omeprazole (CYP2C19) to 5-hydroxyomeprazole, 1.373 (0.864-2.180) for dextromethorphan to dextrorphan (CYP2D6), and 0.824 (0.658-1.032) for midazolam (CYP3A4) to 1-hydroxymidazolam. The geometric mean ratio of the area under the curve of the last sampling time ($AUC_{last}$) for fexofenadine (P-gp) was 0.963 (0.845-1.098). Administration of concentrated RG for 2 wk weakly inhibited CYP2C9 and CYP3A4 and weakly induced CYP2D6. However, no clinically significant drug interactions were observed between RG and CYP and P-gp probe substrates. Conclusion: RG has no relevant potential to cause CYP enzyme- or P-gp-related interactions.