• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.291-297
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• 2016

Cytisine (CYT), a partial agonist of ${\alpha}4{\beta}2-nicotinic$ receptors, has been used for antidepressant efficacy in several tests. Nicotinic receptors have been shown to be closely associated with depression. However, little is known about the effects of CYT on the depression. In the present study, a mouse model of depression, the unpredictable chronic mild stress (UCMS), was used to evaluate the activities of CYT. UCMS caused significant depression-like behaviors, as shown by the decrease of total distances in open field test, and the prolonged duration of immobility in tail suspension test and forced swimming test. Treatment with CYT for two weeks notably relieved the depression-like behaviors in the UCMS mice. Next, proteins related to depressive disorder in the brain region of hippocampus and amygdala were analyzed to elucidate the underlying mechanisms of CYT. CYT significantly reversed the decreases of 5-HT1A, BDNF, and mTOR levels in the hippocampus and amygdala. These results imply that CYT may act as a potential anti-depressant in the animals under chronic stress.

• Advances in Traditional Medicine
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• v.9 no.2
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• pp.135-141
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• 2009

The purpose of this study was to characterize the putative anxiolytic-like effects of the 70% ethanol extract of Portulaca oleracea (EPO) using an elevated plus maze (EPM) in mice. The EPO was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM, respectively. Control mice were treated with an equal volume of 10% tween 80, and positive control mice with diazepam (1 mg/kg). Single treatments of the EPO significantly increased the percentage of time spent and arm entries into the open arms of the EPM versus controls (P < 0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In addition, the anxiolytic-like effects of the EPO were blocked by flumazenil (10 mg/kg, i.p), a $GABA_A$ antagonist not by WAY 100635 (0.3 mg/kg, i.p), a 5-$HT_{1A}$ receptor antagonist. These results indicate that P. oleracea is an effective anxiolytic agent, and suggest that the anxiolytic-like effects of P. oleracea is mediated via the GABAergic nervous system.

• CELLMED
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• v.2 no.4
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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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• v.46 no.6
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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.

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.213-220
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• 2010

Therapeutic duplication (TD) is a serious problem that frequently occurring primarily in the ambulatory setting in Korea. Implementation of concurrent drug utilization review (DUR) is a promising way to reduce inappropriate prescription and dispensing, and improve patient safety. This study was aimed to develop the process of DUR module of TD. Sixty-five drug ingredients classified into the drug category of the antipyretic, analgesic, and anti-inflammatory drug approved in Korea (The KFDA-dess nated classification codes of 114 or 264) were reviewed for this purpose. The drug ingredients (and products) were reclassified based on WHO's Anatomical, Therapeutic and Chemical (ATC) classification system. The clinical practice guidelines, textbooks and product labels on therapeutic uses of these drugs in Korea and several fores n countries were reviewed. If the drugs were categorized into the same therapeutically duplicable class, they were defined not to be used concurrently because the concurrent use was "therapeutically duplicated (unnecessary or even harmful)". Among the studied drug products, the following 5 drug classes were considto beas "therapeutic duplication": (1), on-t tooid DURnti-inflammatory drugs (NSAIDs, including s Dicylates), (2),Anilidts, (3),Opioids, (4) Ergot Dk Doids and (5) 5-$HT_1$ receptor agonot s. Therefore, concurrent prescribing or dispensing of more than 2 drug ingredients any in the above same classes should be considered as TD and needed to be warrant for careful review by pharmacists before dispensing.

• Journal of Oriental Neuropsychiatry
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• v.22 no.2
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• pp.129-146
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• 2011

Objectives : The purpose of this study was to characterize the putative antidepressant and antianxiolytic effects of the 70% ethanol extract of Polygala japonica(EEPJ) using animal's behavioral experiment in mice. Methods : The effect of EEPJ on the anxioty and depressive disorder was investigated via mice's behavioral experiment like Elevated plus-maze, Horizontal wire test, Open field test, Forced swimming test, Tail suspension test, and it was happen via any mechanism by WAY 100635, a 5-HT1A receptor antagonist and by Flumazenil, a GABAA antagonist Results : 1. In the EPM, single treatments of the EEPJ(200 and 400mg/kg) had usefully antianxiolytic effects versus vehicle, which was medicated via the serotonergic nervous system. 2. In the HWT, single treatments of the EEPJ were no changes in the myorelaxant effects versus vehicle. 3. In the OFT, single treatments of the EEPJ were no changes in the locomotor activity versus vehicle. 4. In the FST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. 5. In the TST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. Conclusions : These results indicate that EEPJ is an effective antidepressant and antianxiolytic activity in mice, and it might be usefully applied for prevention and treatment of depressive disorder through evolutive study like development of various experimental models.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.2
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• pp.225-232
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• 2013

Delayed gastrointestinal (GI) motility is frequent adverse effect associated with chemotherapy, and induced by serotonin releases from enterochromaffin cells. Ijintang-gamibang (IJG) is a digestive polyherbal formula has been traditionally used in Korea and consisted of 8 types of medicinal herbs. This study was conducted to determine whether or not IJG aqueous extracts can prevent delayed GI motility induced by the antineoplastic drug cisplatin chronically administered, once per week for five consecutive weeks (2 mg/kg). 200, 100 and 50 mg/kg of IJG extracts were orally administered, once a day for 14 days from fourth cisplatin treatment, and the changes in body weight gain, fecal parameters, gastrointestinal transit ratio and histopathology were observed. In addition, pylorus gastrin and serotonin contents were also measured with immunohistochemical observations of enterochromaffin cells contains gastrin and serotonin, as compared with ondansetron, a serotonin 5-HT3 receptor antagonist, 1 mg/kg. Cisplatin treatment related body weight decreases, delayed GI motility, decreases of fecal water contents were significantly and dose-dependently inhibited by oral treatment of IJG extracts, and they also inhibited the pylorus gastrin and serotonin changes induced by cisplatin treatment. The overall effects of IJG 100 mg/kg were similar to that of ondansetron 1 mg/kg. The present results supported that IJG aqueous extracts have favorable ameliorating effect on the delayed GI motility induced by chemotheraphy, modulated the GI enterochromaffin cells, serotonin and gastrin-producing cells with antioxidant effects. This effect of IJG may help improve accompanying gastrointestinal symptoms by chemotherapy.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.151-156
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• 2004

This study was carried out to evaluate the putative anxiolytic-1ike effects of the aqueous extracts of Sanjoin-tang (SJIT) and its ingredients using the elevated plus maze (EPM) test in mice. SJIT consists of five herbs, namely, Zizyphi Spinosi Semen (roasted), Glycyrrhizae Radix, Cnidii Rhizoma, Anemarrhenae Rhizoma, and Hoelen. The aqueous extracts of SJIT and each herbal drug were orally administered to ICR mice, 1 hr before evaluating behavioral activity in the EPM test, respectively. Repeated treatments (for 3 days) of the aqueous extract of SJIT (400 mg/kg) significantly increased time-spend in the open arms and arms entries into the open arms in the EPM test. Zizyphi Spinosi Semen (400 mg/kg), an ingredient of SJIT, significantly increased timespent in the open arms and arm entries into the open arms (P < 0.05). However, the other ingredient of SJIT did not show any anxiolytic-like behaviors. In addition, the anxiolytic-like effects of Zizyphi Spinosi Semen were blocked by pindolol (lO mg/kg), a $5-HT_{1A}$ receptor antagonist. These results suggest that Zizyphi Spinosi Semen (roasted) as an ingredient of SJIT plays a crucial anxiolytic role, and it acts via the serotonergic nervous system.

• Biomolecules & Therapeutics
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• v.13 no.2
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• pp.84-89
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• 2005

The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of the root of Polygala tenuifolia ( AEPT) using an elevated plus maze (EPM) and hole-board apparatus in mice. The AFPT was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM respectively. Control mice were treated with an equal volume of saline, and positive control mice with buspirone (2 mg/kg). Single treatments of the AEPT significantly increased the percentage of time spent and arm entries into the open arms of the EPM vedrsus saline controls (P<0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In the hole-board test,single treatments of the AEPT (200 and 400 mg/kg) significantly increased the number of headdips versus saline controls (P<0.05). In addition, the anxiolytic-like effects of the AEPT were blocked by WAY 100635(0.3mg/kg, I.p), a5-$HT_{1A}$ receptor antagonist not by flumazenil, a $GABA_{A}$ antagonist. These results indicate that P. tenuifolia is an effective anxiolytic agent, andsuggest that the anxiolytic-like effects of P. tenuifolia is mediated via the serotonergic nervous system.