• 약학회지
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• 제53권3호
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• pp.145-150
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• 2009

We evaluated cytotoxic effect based on the MTT assay and identified altered proteins in 5-FU(fluorouracil) treated HT29 cells using two-dimensional gel electrophoresis and MALDI-TOF/TOF-MS. As proteins inducing apoptosis, siah binding protein 1 and p47 protein isoform a were up-regulated and tumor protein translationally-controlled 1 was down-regulated by 5-FU treatment. And mannose 6 phosphate receptor binding protein 1 controls DNA mismatch repair system was increased. We suggest 5-FU promotes a cytotoxicity under the action of these proteins in colon cancer cells.

• 대한핵의학회지
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• 제31권4호
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• pp.421-426
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• 1997

[$^{18}F$]FMBS는 도파민 $D_2$ 수용체 방사성추적자로서 유망한 성질을 지니고 있다. [$^{18}F$]FMBS는 비교적 높은 특이결합/비특이결합 비를 제공하며, 그 체내결합은 도파민 $D_2$ 수용체에 대하여 높은 특이성과 선택성을 보인다. 도파빈 $D_2$ 수용체 측정을 위한 보다 적합한 PET 방사성추적자를 얻기 위해서는 [$^{18}F$]FMBS의 낮은 뇌섭취와 느린 역학을 개선할 수 있는 화학적 구조의 변형이 시도되어야 하며, [$^{18}F$]FMBS는 이러한 시도의 골격이 될 수 있을 것으로 믿는다.

• Korean Journal of Acupuncture
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• 제23권2호
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• pp.113-123
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• 2006

Objectives: Pharmacopuncture which is a combination of acupuncture and herbal medicine helps to prevent and treat the diseases and symptoms including various pains. However, little was known about the therapeutic effects and its mechanisms on acute pain, although pharmacopuncture has been used frequently in acupuncture clinics. Acupuncture is known for producing analgesia for persistent ankle sprain pain in human. Furthermore, it also produces analgesia in a rat model of ankle sprain pain. Methods: To illuminate the underlying mechanisms of capsaicin pharmacopuncture-induced analgesia, weight bearing force (WBF) was observed on the acute ankle sprained rat model. Ankle sprain was induced in the rat by manually hyper-extending ligaments of the right ankle. Capsaicin pharmacopuncture was applied to SI6 (Yanglo) on the left forelimb (contralateral to the sprained ankle). Results: In behavioral test, capsaicin pharmacopuncture produced marked analgesic effects on acute ankle sprained animals as measured by WBF of the affected limb similar to manual acupuncture. Capsaicin pharmacopuncture was also suppressed by serotonin (5-HT) receptor antagonist methysergide (2 mg/kg, Lp.), but not by opioids receptor antagonist naltrexone (10 mg/kg, Lp.) and alpha adrenoceptor antagonist phentolamine (5 mg/kg, Lp.). Conclusion: The data suggest that capsaicin pharmacopuncture-induced analgesia is accomplished by activating the descending serotonergic inhibitory systems.

• Mass Spectrometry Letters
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• 제9권3호
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• pp.86-90
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• 2018

Methallylescaline, 2-(3,5-dimethoxy-4-[(2-methylprop-2-en-1-yl)oxy]phenyl)ethanamine, is a new psychoactive substance with potent agonist of 5-HT receptor, but there is little information on its pharmacological effect, metabolism, and toxicity. It is necessary to characterize the metabolic profiling of methallylescaline in human hepatocytes using liquid chromatography-high resolution mass spectrometry. Methallylescaline was metabolized to three hydroxy-methallylescaline (M1-M3) and dihydroxy-methallylescaline (M4) via hydroxylation in human hepatocytes. CYP2D6, CYP2J2, CYP1A2, and CYP3A4 enzymes were responsible for the metabolism of methallylescaline. The metabolites as well as methallylescaline would be used for monitoring the abuse of methallylescaline.

• 셀메드
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• 제2권4호
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• pp.38.1-38.6
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• 2012

The present study aimed to determine the possible mechanisms of the peripheral antinociception of the aqueous extracts of Dicranopteris linearis (AEDL), Melastoma malabathricum (AEMM) and Bauhinia purpurea (AEBP) leaves in mice. Briefly, the antinociceptive profile of each extract (300, 500, and 1000 mg/kg; subcutaneous (s.c.)), was established using the abdominal constriction test. A single dose (500 mg/kg) of each extract (s.c.) was pre-challenged for 10 min with various pain receptors' antagonists or pain mediators' blockers and 30 min later subjected to the antinociceptive assay to determine the possible mechanism(s) involved. Based on the results obtained, all extracts exerted significant (p < 0.05) antinociceptive activity with dose-dependent activity observed only with the AEMM. Furthermore, the antinociception of AEDL was attenuated by naloxone, atropine, yohimbine and theophylline; AEMM was reversed by yohimbine, theophylline, thioperamide, pindolol, reserpine, and 4-chloro-DL-phenylalanine methyl ester hydrochloride; and of AEBP was inhibited by naloxone, haloperidol, yohimbine and reserpine. In conclusion, the antinociceptive activity of those extracts possibly involved the activation of several pain receptors (i.e. opioids, muscarinic, ${\alpha}_2$-adrenergic and adenosine receptors, adenosine, H3-histaminergic and $5HT_{1A}$, dopaminergic receptors).

• Tuberculosis and Respiratory Diseases
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• 제46권6호
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• pp.811-816
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• 1999

Background : Nausea and vomiting associated with chemotherapy are common side effects which remain difficult to control. Acute phase nausea and vomiting (0-24 hours after induction of chemotherapy) parallels plasma serotonin release, which explains the effectiveness of $5-HT_3$ receptor antagonists. Serotonin released from gastrointestinal enterochromaffin cells may mediate chemotherapy-induced emesis. In this study, we analyzed urinary excretion of 5-HIAA, the main metabolite of serotonin. Methods : Eight men and four women were studied in their cisplatin chemotherapy cycle. Urinary 5-hydroxyindoleaoetic aicd (HIAA) levels were determined before and during a 24-hour period under ondansetron prophylaxis. Results : Urinary 5-HIAA excretion for a 24-hour period was increased in all patients after induction of cisplatin (P=0.002). Conclusion : Cisplatin chemotherapy is associated with serotonin release in the acute phase. Our finding may provide evidence for a relationship between emesis and serotonin following cisplatin chemotherapy.

• The Korean Journal of Pain
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• 제14권1호
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• pp.46-50
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• 2001

Background: Ondansetron is both a central and peripheral serotonin (5HT) receptor antagonist and droperidol is a dopaminergic blocking drug which acts centrally at the chemoreceptor trigger zone. We assessed the efficacy and adverse effects of ondansetron, droperidol or both, in the prevention of postoperative emesis during postoperative intravenous patient-controlled analgesia (PCA) using butorphanol and ketorolac medication. Methods: We studied 60 women, aged 25-60 yrs, who underwent total abdominal hysterectomy (TAH), under general anesthesia using $N_2O-O_2$-enflurane. A bolus dose of 1 mg of butorphanol and 4 mg of ondansetron were given to patients and thereafter, PCA was started using 10 mg of butorphanol and 240 mg of ketorolac mixed into the 5% D/W solution (total volume; 100 ml, 1 ml of bolus dose, and 10 min of lockout interval). We also added ondansetron 4 mg (Group O, n = 20), ondansetron 4 mg and droperidol 2.5 mg (Group OD, n = 20), or droperidol 2.5 mg (Group D, n = 20) to the PCA drug. The severity of pain, nausea, vomiting, sedation and other side effects were assessed at 0, 1, 2, 6, 12, 24, 36 and 48 hr after awakening. Results: There was no difference in the incidence of nausea and vomiting between the three group [Group O: 4 (20%) and 3 (15%), respectively; Group OD: 1 (5%) and 1 (5%), respectively; Group D: 3 (15%) and 3 (15%), respectively]. Group O showed a lower sedation score than the other groups (P < 0.05). The pain score and other side effects did not show any difference between the groups. Conclusions: The combination of ondansetron and droperidol showed no clinical benefit compared with ondansetron or droperidol alone for prevention of postoperative nausea and vomiting during postoperative PCA using butorphanol and ketorolac.

• Journal of Pharmaceutical Investigation
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• 제36권6호
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• pp.363-369
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• 2006

Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although this drug is commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liquid chromatography method with mass spectrometric detection(LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. This method has been validated for concentrations ranging from 5 to 1000 ng/ml with simple treatment. This technique has high level reproducibility, accuracy, and sensitivity. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. This study was aimed to investigate the feasibility of nasal delivery of granisetron for the elimination of vomiting. The effects of osmolarity, dosage volume at the same dose and applied dose on the nasal absorption of granisetron in rats were observed. No significant difference in the effect of osmolarity and dosage volume at the same dose was observed. As the applied dose of granisetron in nasal formulation increased, the absorption increased linearly. Based on these results it appears that only the applied dose(drug mass) determines the nasal absorption of granisetron. The bioavailability of granisetron on nasal administration of 4 mg/kg appeared to be comparable to that of intravenous administration of the same dose. These results suggest that granisetron can be efficiently delivered nasally and the development of nasal formulation will be feasible.

• 생물정신의학
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• 제6권2호
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• pp.193-201
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• 1999

This study was designed to evaluate the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessivecompulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injection group with experimental drug treatment for 21 days. The effects on the 5-MeODMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows ; 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. We indentified that the opioid kappa agonist that act as dopamine release inhibitor affect the spontaneous alternation behaviour which is an animal model of obsessive-compulsive disorder in rat.

• 대한한방내과학회지
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• 제30권1호
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• pp.107-118
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• 2009

Objectives : This study was aimed to investigated the effect of Yijin-tang on gastric motility and its mechanism of action in normal intact and partial pyloric obstructed rats. Methods : Gastric emptying was measured by the number of glass beads expelled from the stomach (containing one hundred of glass beads. ${\phi}1mm$) in 1 hour or 2 hours after glass beads and test drugs (normal saline. Yijin-tang 90mg/kg. Yijin-tang 270mg/kg) administration in normal intact and partial pyloric obstructed rats. In another series of experiments to evaluate the mechanism of Yijin-tang 270mg/kg under delayed conditions, normal intact rats were treated with atropine sulfate (1mg/kg,s.c.), cisplatin (10mg/kg,i.p.), quinpirole HCI (0.3mg/kg,i.p.) and NAME (NG-nitro-L-arginine methyl ester. 75mg/ kg,s.c.), respectively. Partial pyloric obstructed rats were modified by wrapping the nonabsorbable rubber ring (D :6mm, W:4mm, T: 1mm) around the 1st portion of the duodenum for 8 weeks. The myoelectrical activity of the gastric smooth muscle was recorded by a bipolar electrode placed at the abdominal surface in normal intact and partial pyloric obstructed rats. The gastric myoelectrical activity was measured for 30 minutes before and after orogastric administration of each solution (normal saline, Yijin-tang 270mg/kg) and expressed as dominant frequency, percent of normogastria and power ratio. Results : Yijin-tang improved gastric emptying more than normal saline in normal intact(p<0.001) and partial pyloric obstructed rats(p=0.002). Under the delayed gastric emptying induced by atropine sulfate, cisplatin, quinpirole HCI and NAME. Yijin-tang enhanced gastric emptying significantly in the cisplatin treated group(p<0.001). but didn't in other treated groups. Administration of Yijin-tang 270mg/kg has no significant effect on the myoelectrical activity of the gastric smooth muscle in both normal intact rats and partial pyloric obstructed rats. Conclusions : Yijin-tang seems to stimulate the gastric motility through suppressing the 5HT3 receptor and promoting the antroduodenal flow. We expect that Yijin-tang would be effective especially in dysmotility-like functional dyspepsia with partial pyloric obstruction or the side effects of cisplatin such as nausea, vomiting, abdominal discomfort, and delay of gastric emptying.