• 약학회지
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• 제41권3호
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• pp.277-282
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• 1997

Methamphetamine, which is the most commonly abused drug in Korea, exists in terms of d-, l- isomers and a racemate(dl). d-Methamphetamine is a potent central nervous system stimulant, whereas l-Methamphetamine is sold freely as a nasal decongestant. In addition, methamphetamine appears in different ratios of optical isomers by the clandestine synthesis applied. In this study, enetiomeric separation of methamphetamines was estabilished to distinguish the chirality of methamphetamines trafficked and abused in Korea. A gas chromatograph/mass spectrometer(GC/MS) system equipped with an achiral capillary column is used to isolate the isomers of methamphetamine after (S)-N-(trifluoroacetyl)-l-prolyl(TFP) deravatization.After analyzing 10 illicit methamphetamine powders and 10 positive urine samples, following findings were found: d-Methamphetamine was well resolved from l-Methamphetamine by chromatographic separation of TFP derivatibes on DB-5 with retention time of 11.80 and 11.35 min respectively. The detection of d-Methamphetamine in all 10 powders and 10 urine samples proves that all methamphetamines abused in Korea are illegally manyfactured and administred.

• 약학회지
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• 제41권6호
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• pp.698-703
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• 1997

Recently, l-deprenyl (selegiline), a relative new antiparkinson`s drug, has been marketed in Korea. As its metabolites, l-methamphetamine and l-amphetamine, are the enantiomers of illicit drugs,d-methamphetamine and d-amphetamine, a method for analysis of enantiomers of methamphetamine and amphetamine in rat urine was investigated. The optical isomers of methamphetamine and amphetamine were analyzed with the chiral derivatizing reagent (S)-(-)-N-(trifluoroacetyl)-prolyl chloride (l-TFP), which was used to form the diastereomers of methamphetamine and amphetamine. And all diastereomers (l-TFP -l-AM, lTFP-d-AM, l-TFP-l-MA & l-TFP-d-MA) were well resolved by capillary gas chromatography. After administration of 10mg/kg l-deprenyl to rat, l-methamphetamine and l-amphetamine were detected without autoracemization to the d form in all urine samples collected during 24hrs, and the ratios of l-amphetamine/l-methamphetamine were 1.1~3.3. l-Amphetamine was detected in only 3 out of 8 urine samples collected during 24~48hrs where as no l-methamphetamine was detected in all cases.

• 약학회지
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• 제42권1호
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• pp.101-107
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• 1998

The antiparkinsonian agent l-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, is metabolized in part to l-methamphetamine and l-amphetamine. l< /I>-Deprenyl was evaluated for amphetamine and methamphetamine-like discriminative stimulus effects in rats and its mechanism of action was investigated. Rats were trained under a 5-response, fixed ratio schedule of stimulus-shock termination or a 10-response. Fixed-ratio schedule of food-presentation which discriminate between d-amphetamine (1mg/kg, i.p.) and saline or d-methamphetamine (1mg/kg, i.p.) and saline in a two-lever, operant conditioning procedure. Full generalization was obtained to d-amphetamine (1~3mg/kg). d-methamphetamine (1~3mg/kg) and l-deprenyl (17~30mg/kg) under both the food presentation and stimulus shock termination schedule. l-Deprenyl has dose-dependent amphetamine-and methamphetamine-like discriminative stimulus properties in rats only at doses of 17 and 30mg/kg. Reversible MAO-B inhibitor, RO 16-6491 didn`t show any amphetamine-like discriminative properties. Aromatic amino acid decarboxylase inhibitor, NSD 1015 decreased % responding of l-deprenyl in the methamphetamine-trained rats under the stimulus-shock termination schedule. SKF-525A produced partial inhibition of methamphetamine-like discriminative effects of l-deprenyl under the food presentation schedule. These results suggest that l-deprenyl has no abuse liability at the therapeutic range but there needs some caution at high doses and furthermore, drug discrimination studies under the food presentation and shock termination schedule are useful for the assessment of abuse liability of psychostimulants.

• 약학회지
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• 제37권4호
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• pp.356-361
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• 1993

A sensitive method for the determination of methamphetamine(MA) and amphetamine(AM) in hair was developed by gas chromatography/mass spectrometry using stable isotope-labeled internal standards, amphetamine-d$_{5}$ and methamphetamine-d$_{5}$. Hair sample was washed with MeOH, incubated with MeOH(I% HCI) overnight at $37^{\circ}C$ while stirring and extracted using solid phase extraction column on a vacuum manifold. The extract obtained was pentafluoropropionated, and applied to GC/MS. The calibration curves of MA and AM were linear from 2.5 to 250 ng (r>0.99 for both). The limit of detection was 0.1 ng/mg in hair and cut-off level was set at 0.25 ng/mg for both. Hair samples of 27 MA abusers showed positive results in the range 0.7 to 106.8 ng/mg. AM, its metabolite, was detected in 20 out of 27 samples. The ratio of MA versus AM was 4.6~38.3 in specimens. Hair analysis for methamphetamine by GC/MS is an effective method for identifying long-term drug abusers.

• Biomolecules & Therapeutics
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• 제12권2호
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• pp.101-107
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• 2004

Repeated administration of psychostimulants such as amphetamines increases locomotor activity in rodents. These drugs, including methamphetamine, enhance dopaminergic neurotransmission and result in hyper-locomotion and behavioral sensitization. It is well known that the existence of a complex balance between the cholinergic and dopaminergic systems in the central nervous system. Thus, behavioral sensitization by methamphetamine may be related to the expression of the M1 muscarinic acetylcholine receptors gene. The present study investigated the changes of M1R mRNA in hyperlocomotor activity and behavioral sensitization by methamphetamine (2 mg/kg) in mice. Our results showed that M1R mRNA expression was increased in the frontal cortex and the hippocampus region (the CA2 region) in the acute methamphetamine administered group compared to the saline administered group. In the chronic group, M1R mRNA expression was increased in the frontal cortex ill1d the hippocampus regions (CA2 and DG regions) in melt1amphetamine administered group compared to saline control group. These results indicate that acute or chronic treatment of mathamphetamine leads to the region-specific changes in mRNA expression levels of M1R. Therefore, Therefore, the present result suggests that M1R may play a role in modulating of methamphetamine-induced behavioral sensitization in mice.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.102-102
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• 1995

The present study was undertaken to investigate the behavioral and biochemical effects of ginseng total sponin (GTS) on methamphetamine-treated mice. GTS (50 or 100 mg/kg) was administered intraperitoneally two times with 2 hour interval. Two hours after the second injection of GTS, methamphetamine (2 mg/kg) was administered subcutaneously. The ambulatory activity of mice was measured by the ti1ting-type ambulometer every 10 min. for 1 hour. Methamphetamine-induced hyperactivity was reduced by GTS. in a dose-dependent manner. To study the neurochemical mechanism underlying the GTS effects, monoamine contents were measured from brain tissues. After 45 min. of methamphetamine injection. mice were sacrificed and monoamine contents were determined from the striatum. Biochemical analysis revealed that GTS reduced the methamphetamine- induced increase in striatal dopamine contents. These observations indicate that inhibition of methamphetamine-induced hyperactivity by GTS is mediated by the modulation of dopaminergic nervous system, and it could be helpful for the therapy of hyperactivity.

• 대한핵의학회지
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• 제35권4호
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• pp.258-267
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• 2001

Purpose/Methods: Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum uslng $[^3H]$]WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Results: Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 mg/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4 mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. Conclusion: These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli.

• 분석과학
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• 제32권5호
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• pp.163-172
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• 2019

Methamphetamine (MA) is currently the most abused illicit drug in Korea and its major metabolite is amphetamine (AP). As MA exist as two enantiomers with the different pharmacological properties, it is necessary to determine their respective amounts in a sample. Thus a chiral stationary phase liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for identification and quantification of d-MA, l-MA, d-AP, and l-AP in human urine. Urine sample ($200{\mu}L$) was diluted with pure water and purified using solid-phase extraction (SPE) cartridge. A $5-{\mu}L$ aliquot of SPE treated sample solution was injected into LC-MS/MS system. Chiral separation was carried out on the Astec Chirobiotic V2 column with an isocratic elution for each enantiomer. Identification and quantification of enantiomeric MA and AP was performed using multiple reaction monitoring (MRM) detection mode. Linear regression with a $1/x^2$ as the weighting factor was applied to generate a calibration curve. The linear ranges were 25-1000 ng/mL for all compounds. The intra- and inter-day precisions were within 3.6 %, while the intra- and inter-day accuracies ranged from -5.4 % to 11.8 %. The limits of detection were 2.5 ng/mL (d-MA), 3.5 ng/mL (l-MA), 7.5 ng/mL (d-AP), and 7.5 ng/mL (l-AP). Method validation parameters such as selectivity, matrix effect, and stability were evaluated and met acceptance criteria. The applicability of the method was tested by the analysis of genuine forensic urine samples from drug abusers. d-MA is the most common compound found in urine and mainly used by abusers.

• 분석과학
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• 제26권4호
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• pp.228-234
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• 2013

국내에서 불법 유통 되거나 남용되고 있는 methamphetamine은 아민을 함유한 불법약물로서 그에 대한 신속하고 용이한 동정 및 정량적인 분석 방법은 불법약물 검사의 중요한 이슈가 되어왔다. 새로운 screening방법을 모색하기 위해 methamphetamine과 구조적으로 유사한 3종의 유기 화합물을 silica gel ($SiO_2$) TLC상에서 N-(9-Fluorenylmethoxycarbonyloxy)succinimide (FMOC-NHS)와 반응을 시켰다. TLC상 반응 생성물을 일반 유기합성 경로로 합성한 대조물질과 비교 확인한 다음, 이 방법의 검출한계(Limit of detection)를 조사하였다. 실험결과 유도체화 시약으로 사용한 FMOC-NHS는 TLC상에서 1차 및 2차 아민과 반응하여 UV-active한 화합물을 생성시키는 것을 확인하였다. 2D TLC 실험에서는 0.045-0.01 mg/mL ($2{\mu}L$ per spot), 그리고 1D co-spot TLC 실험에서 0.002-0.007 mg/mL ($2{\mu}L$ per spot)의 검출한계는 유도체화 시약의 농도에 대한 의존성을 나타내었다.

• Journal of Ginseng Research
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• 제46권1호
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• pp.147-155
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• 2022

Background: Methamphetamine (METH) is the most widely used psychostimulant and has been known to exhibit reinforcing effects even after long abstinence. We showed the inhibitory effect of Korean Red Ginseng extract (RGE) on METH-induced addictive behaviors in animal models mimicking the human drug-use pattern. Methods: We first investigated the effect of RGE on the acquisition of METH-induced dependence using self-administration and conditioned place preference (CPP) tests. Additionally, further experiments such as METH-induced motivational behavior and seeking behavior were conducted. To study the underlying mechanism, dopamine receptor, dopamine transporter, and N-methyl-D-aspartate receptor were assessed through Western blot analysis. Results: Treatment with RGE significantly reduced METH-induced self-administration on a fixed-ratio 1 schedule of reinforcement. It could be also decreased a progressive ratio schedule, and inhibited METH-primed reinstatement. In CPP, RGE significantly prevented the development of METH-induced CPP. Moreover, RGE not only shortened the withdrawal period clearly, but also prevented the reinstatement of CPP. RGE treatment also reversed METH-induced overexpression of dopamine transporter, dopamine receptor D1, and NMDA receptor in the nucleus accumbens. Conclusion: Our findings reflect that RGE has therapeutic potential to suppress METH-induced addictive behaviors by regulating dopaminergic and NMDAergic system.