• Archives of Pharmacal Research
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• 제11권2호
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• pp.122-126
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• 1988

The effects of psoralen and angelicin on hepatic microsomal drug-metabolizing enzyme (DME) activities were investigated to elucidate the mode of the interaction of furanocoumarins with DME system. A single administration (30 mg/kg,i. p.) of both coumarins to mice cased a significant prolonagation of hexobarbital-induced hypnosis as well as an increase in strychnine toxicity. The inhibitory potencies of both coumarins as measured by rat hepatic microsomal aminopyrine N-demethylase and hexobarbital hydroxylase activities in vitro were considerably weaker than those of other furanocoumarins which possess a side chain moiety. Both coumarins were found to have significant inducing effects of DME system, with repeated treatments of them. The activities of an angular coumarin were stronger than those of a linear coumarin.

• 생명과학회지
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• 제26권1호
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• pp.123-128
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• 2016

본 연구의 최종 목표는 한방제제인 심적환과 심혈관계 양방 치료제인 cilostazol과 병용 투여 효과에 대한 포괄적이고 통합의학 측면에서 정확한 정보를 얻는 것이다. Cilostazol은 말초 동맥질환 치료제로 개발 된 항 혈소판 및 혈관확장제이다. 사이클릭 AMP protein kinase A를 활성 시켜 세포내 사이클릭 AMP (cAMP) 증가를 통하여 내피세포의 NO생산을 활성화 시킨다. 심적환을 단 회 또는 반복 투여 후 cilostazol의 약물 동태학적 효과를 평가하기 위하여 순수한 증류수 단회 용량과 증류수에 심적환 콜로이드 현탁액을 각각 대조군과 시험군에 투여 하여 30분 후, 두 그룹에 cilostazol를 투여하였다. 혈청은 cilostazol 약물 투여 30분 전에 수집 하였으며, cilostazol 약물 처리 후 0.25, 0.5, 0.45 및 1, 2, 4, 6, 8, 24시간 후에 각각 수집 하였다. 그 다음 실험군과 및 테스트 그룹 사이에 실로 스타 졸에서 관찰 된 약동학 적 변화를 평가 하였다. 통계적으로 유의 한 차이는 심적관 단독 투여와 반복투여군 그룹의 약물 동태 학에서 관찰되지 않았다. 이러한 연구 결과는 만성 질환 환자에서 한약제인 심적환의 투여는 cilostazol의 약동학에 영향을 미치지 않았음을 보여 주었다. 본 연구에서 얻어진 결과는 만성 혈관질환 환자에서 심적환과 cilostazol의 병용 투여를 제안하며 두 약물간의 잠재적 인 약물 상호 작용에 대한 cilostazol의 생체 이용률에 영향을 미치지 않을 것이라 판단된다.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.201-209
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• 2018

G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.

• Journal of Dental Anesthesia and Pain Medicine
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• 제21권4호
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• pp.345-355
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• 2021

Background: This study aimed to evaluate the efficacy of external vibrating devices and counterstimulation on a child's dental anxiety, apprehension, and pain perception during local anesthetic administration. Methods: This was a prospective, randomized, parallel-arm, single-blinded interventional, clinical trial. One hundred children aged 4-11 years, requiring pulp therapy or extraction under local anesthesia (LA), were recruited and allocated equally into two groups (1:1) based on the interventions used: Group BD (n = 50) received vibration using a Buzzy^® device {MMJ Labs, Atlanta, GE, USA} as a behavior guidance technique; Group CS (n = 50) received counterstimulation for the same technique. Anxiety levels [Venham's Clinical Anxiety Rating Scale (VCARS), Venham Picture Test (VPT), Pulse oximeter {Gibson, Fingertip Pulse Oximeter}, Beijing, China)] were assessed before, during, and after LA administration, while pain perception [Wong-Baker Faces Pain Rating Scale (WBFPS), Visual Analogue Scale (VAS)] was evaluated immediately after injection. Statistical analysis was performed using the Student's t-test to assess the mean difference between the two groups and the repeated measures ANOVA for testing the mean difference in the pulse rates. Statistical significance was set at P < 0.05. Results: Significant differences in mean pulse rate values were observed in both groups. In contrast, the children in the BD group had higher diminution (P < 0.05), whereas the mean VCARS and VPT scores were conspicuous (P < 0.05). Based on the mean WBFPS and VAS scores, delayed pain perception after LA injection was more prominent in the BD group than in the CS group. Conclusion: External vibration using a Buzzy^® device is comparatively better than counterstimulation in alleviating needle-associated anxiety in children requiring extraction and pulpectomy.

• 약학회지
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• 제43권1호
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• pp.33-41
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• 1999

Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.

• 대한약침학회지
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• 제18권2호
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• pp.76-85
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• 2015

Objectives: Radix Ginseng has been traditionally used as an adaptogen that acts on the adrenal cortex and stimulates or relaxes the nervous system to restore emotional and physical balance and to improve well-being in cases of degenerative disease and/or old age. Radix Ginseng has been used for a long time, but the safety of ginseng pharmacopuncture needs testing. This study was done to analyze the single-dose toxicity of water- soluble ginseng pharmacopuncture (GP) intramuscular injections in rats. Methods: All experiments were performed at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP). Each group contained 10 Sprague-Dawley rats, 5 males and 5 females. GP was prepared in a sterile room at the Korean Pharmacopuncture Institute under regulations of Good Manufacturing Practice (GMP). GP dosages were 0.1, 0.5 and 1.0 mL for the experimental groups; normal saline was administered to the control group. The animals general condition was examined daily for 14 days, and the rats were weighed on the starting day and at 3, 7 and 14 days after administration of the pharmacopuncture. Hematological and biochemistry tests and autopsies were done to test the toxicological effect of GP after 14 days. This study was performed with approval from the Institutional Animal Ethics Committee of Biotextech. Results: No deaths were found in this single-dose toxicity test of intramuscular injections of GP, and no significant changes in the general conditions, body weights, hematological and biochemistry tests, and autopsies were observed. The local injection site showed no changes. Based on these results, the lethal dose was assumed to be over 1.0 mL/animal in both sexes. Conclusion: These results suggest that GP is relatively safe. Further studies, including a repeated toxicity test, are needed to provide more concrete evidence for the safety of GP.

• 동의생리병리학회지
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• 제26권2호
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• pp.189-198
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• 2012

Our former study indicated efficacy of apoptotic cell death on animal study by using Egg white combined Chalcanthite (EC). Clinically, bamboo salt is using because of safety. Hence we investigated a toxicity study for determining safety by adding bamboo salt in former materiel. We had two studies: toxicity of EC and of Bamboo salt with egg white combined Chalcanthite (BC). Both were studied in 1-week single and 5-week repeated oral dose toxicity tests on male Imprinting Control Region mice. In EC, doses used in 1 week single oral dose toxicity tests were 0, 0.05, 0.5, 5 and 50 mg/kg/day and 0, 0.01, 0.05, 0.25 and 0.5 mg/kg/day. In BC, doses used by 0, 0.08, 8.3, 83.3 and 166.6 mg/kg/day in single oral dose toxicity and 0, 4.2, 8.3, 41.7 and 83.3 mg/kg/day in repeated oral dose toxicity tests. Their blood and urine were assayed and organ morphology were examined. Mann-Whitney U test and ANOVA tests were used by analysing methods. First, significant increased left renal weight in all groups of EC and BC. Second, increased ALT score was found in EC-S2 and increased relative liver weight was found in EC-S3. In addition, increased relative weight and urine bilirubin and urobilinogen were found in EC-R2 and EC-R3. There was no significant toxic change in BC. The Mixture of EC had a possibility of hepatotoxicity in the short and long term. Processed BC appears to be safe and non-toxic in these studies and a no-observed adverse effect level (NOAEL) was established at 83.3 mg/kg/day in mice. Relatively, The BC were safer than The EC.

• 동의생리병리학회지
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• 제17권2호
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• pp.510-517
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• 2003

Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and it is suggested that both of these effects are mediated by the same or closely overlapping dopamine systems. Specifically, the mesolimbic dopamine system has been implicated in the reinforcing and sensitizing properties of morphine. In oriental medicine, Shenmen (HT7) point on the heart channel has been used to treat mental and psychosomatic disorders. This study was designed to investigate the effect of acupuncture on acute and repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and morphine-induced behavioral changes. In the morphine sensitization experiment, male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5 mg/kg, s.c.). Acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after the morphine challenge. In the acute experiment, rats also received acupuncture for 1 min after an injection of morphine hydrochloride (5 mg/kg, s.c.). Results showed that acupuncture at the specific acupoint HT7, but not at control points (tail) significantly decreased both dopamine release and behavior induced by a systemic morphine challenge or a single sc morphine injection in the acute animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts.

• 동의신경정신과학회지
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• 제14권1호
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• pp.85-106
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• 2003

Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and it is suggested that both of these effects are mediated by the same or closely overlapping dopamine systems. Specifically, the mesolimbic dopamine system has been implicated in the reinforcing and sensitizing properties of morphine. In oriental medicine, Shenmen (HT7) point on the heart channel has been used to treat mental and psychosomatic disorders. This study was designed to investigate the effect of acupuncture on acute and repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and morphine-induced behavioral changes. In the morphine sensitization experiment, male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5mg/kg, s.c.). Acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after the morphine challenge. In the acute experiment, rats also received acupuncture for 1 min after an injection of morphine hydrochloride (5 mg/kg, s.c.). Results showed that acupuncture at the specific acupoint HT7, but not at control points (tail) significantly decreased both dopamine release and behavior induced by a systemic morphine challenge or a single sc morphine injection in the acute animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts.

• 한국식품영양과학회지
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• 제45권10호
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• pp.1406-1413
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• 2016

상지추출물의 독성을 복귀돌연변이, 단회투여 및 반복투여 독성 등 다각적으로 적용하여 평가하였다. 상지추출물의 복귀돌연변이 실험을 Salmonella Typhimurium의 히스티딘 요구성 균주 4종과 Escherichia coli의 트립토판 요구성 균주 1종을 이용하여 대사활성계 적용 및 비적용 하에서 Ames test를 실시하였다. 대사활성계 유무에 상관없이 $5,000{\mu}g/plate$의 처리 농도까지 복귀돌연변이 콜로니 수는 증가되지 않았으므로 상지추출물은 복귀돌연변이를 유발하지 않는 것으로 판단하였다. SD rats 암수에 1,250, 2,500 및 5,000 mg/kg의 농도로 단회 경구투여 하고 14일 동안 일반증상, 운동성, 식이섭취량, 사망 여부 및 체중 변화를 조사한 결과, 사망동물은 관찰되지 않았으며 대조군과 비교하여 실험동물의 암수 모두에서 시험물질 투여에 따른 일반적인 증상변화는 나타나지 않았다. 대조군과 시험군은 모두 정상적인 체중 증가가 관찰되었고 대조군과 비교하여 상지추출물 투여군의 유의적인 체중 변화는 나타나지 않았으며, $LD_{50}$은 암수 모두 5,000 mg/kg 이상인 것으로 판단하였다. 또한, 상지추출물을 500, 1,000 및 2,000 mg/kg/d의 용량으로 28일간 반복 경구투여 하면서 실험동물의 일반증상, 사망동물의 유무, 체중 변화, 식이섭취량, 혈액학적 및 혈액생화학적 변화, 부검 후 육안적 검사를 통한 병변의 유무를 관찰하였다. 시험기간 동안 암수 모든 군에서 반복 투여로 인한 사망동물이 없었으며 정상적인 체중 증가가 나타났다. 대조군과 비교하여 상지추출물의 투여에 따른 체중 변화는 통계학적으로 유의성이 없었으며 암수 모두 대조군과 비교하여 식이섭취량의 차이 및 유의할만한 일반증상도 관찰되지 않았다. 시험물질의 투여에 따른 장기 무게, 혈액학적 분석 결과 및 혈액생화학적 분석 결과 등에서도 독성 및 이상소견이 발견되지 않았다.