• The Korean Journal of Pharmacology
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• v.20 no.2
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• pp.15-21
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• 1984

It was aimed to study the effects of ${\alpha}_2-adrenoceptor$ agonists on the sleeping time in $one{\sim}two-day-old$ chickens. Furthermore, it was also evaluated whether ${\alpha}_1-adrenoceptor$ agonist and antagonist might affect the sleeping in the chickens and discussed in relation with opiate receptor. 1) Guanabenz, clonidine, guanfacine and B-HT 933 decreased the latency of the loss of righting reflex in a dose-dependent manner, but B-HT 920 and oxymetazoline slightly prolonged it. 2) ${\alpha}_2-Adrenoceptor$ agonists produced dose·related increase in sleeping time. The potency was guanabenz>clonidine>oxymetazoline${\geq}$B-HT 933${\geq}$B-HT 920>guanfacine in this order. 3) ${\alpha}_2-Adrenoceptor$ antagonists decreased guanabenz-induced sleeping time in a dose ·dependent manner. The rank order of ${\alpha}_2-adrenoceptor$ antagonists was yohimbine>rauwolscine>piperoxan${\geq}$RX 781094. 4) Sleeping time caused by both ethanol and hexobarbital was not affected by yohimbine in chickens. 5) Methoxamine and phenylephrine showed little significant effect on the guanabenz-induced sleeping time. However, prazosin increased it. Paradoxically, corynanthine rather caused to decrease it. These results suggest that the stimulation of central ${\alpha}_2-adrenoceptor$ mediates sleeping, however it is remained uncertain in the role of central ${\alpha}_1-adrenoceptor$ in chickens. In addition, the one~two-day-old chickens may be considered as a useful, inexpensive and simple experimental model to evaluate the in vivo pharmacological action of the ${\alpha}_2-adrenoceptor$ agonist and antagonist related to sedation.

• 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.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.34-45
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• 1998

We provide the reader with a brief introduction to the neurobiology of neuropeptides. Several comprehensive reviews of the distribution and neurochemical, neurophysiological, neuropharmacological and behavioral effects of the major neuropeptides have recently appeared. In reviews of the large number of neuropeptides in brain and their occurance in brain regions thought to be involved in the pathogenesis of major psychiatric disorders, investigators have sought to determine whether alternations in neuropeptide systems are associated with schizophrenia, mood disorders, anxiety disorders, alcoholism and neurodegenerative disease. There is no longer any doubt that neuropeptide-containing neurons are altered in several neuropsychiatric disorders. One of the factors that has hindered neuropeptide research to a considerable extent is the lack of pharmacological agents that specifically alter the synaptic availability of neuropeptides. With the exception of naloxone and naltrexone, the opiate-receptor antagonists, there are few available neuropeptide- receptor antagonists. Two independent classes of neuropeptide-receptor antagonists has been expected to be clinically useful. Naltrexone, a potent ${\mu}$-receptor antagonist, has been used successfully to reduce the need for alcohol consumption. And cholecycstokinin antagonists are now in development as a new class of anxiolytics, which would be expected to be free from tolerance and physical dependence and lack of sedation. In this review, we deal with these two kinds of neuropeptide system, the opioid system and cholesystokinins in the brain. The role of opioid systems in the reinforcement after alcohol consumtion and that of cholesystokinins in the pathogenesis of anxiety will be discussed briefly. As we know, the future for neuropeptides in psychiatry remains bright indeed.

• The Korean Journal of Pain
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• v.14 no.1
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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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• 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.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.213-218
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• 2000

Ondansetron is a potent, highly selective 5-hydroxytryptamine3(5-HT3) receptor- antagonist, for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiography, and the treatment of post-operative nausea and vomiting. The purpose of the present study was to evaluate the bioequivalence of two ondansetron tablets, $Zofran^{TM}$, (Glaxo Wellcome Korea Ltd.) and Hana ondansetron (Hana Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.56{\pm}1.79$ year in age and $67.35{\pm}8.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 8 mg of ondansetron was orally administered, blood was taken at predetermined time intervals and the concentrations of ondansetron in serum were determined using HPLC with UV detector. Pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets were 7.53%, -0.23% and -3.92%, respectively when calculated against the $Zofran^{TM}$, tablet. The powers $(1-{\beta})$ for $AUC_t,\;C_{max}\;and\;T_{max}$ were above 99.00%, above 99.00% and 84.99%, respectively. Minimum detectable differences $(\Delta)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ were all less than 20% (e.g., 12.25%, 10.88% and 18.37% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The 90% confidence intervals were all within ${\pm}20%$ (e.g., $-0.70{\sim}15.76,\;-7.53{\sim}7.08\;and\;-16.27{\sim}8.42\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). All of the above parameters met the criteria of KFDA for bioequivalence, indicating that Hana ondansetron tablet is bioequivalent to $Zofran^{TM}$, tablet.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.135-146
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• 1993

Background: In acute pulmonary embolism it has been postulated that the constriction of bronchi and pulmonary artery secondary to neurohumoral response plays an important role in cardiopulmonary dysfunction in addition to the mechanical obstruction of pulmonary artery. Serotonin is considered as the most important mediator. Positive end expiratory pressure (PEEP) stimulates $PGI_2$ secretion from the vascular endothelium, but its role in acute pulmonary embolism is still in controversy. Methods: To study the cardiopulmonary effect and therapeutic role of Ketanserin, selective antagonist of 5-HT2 receptor, and PEEP in acute pulmonary embolism experimental acute pulmonary embolism was induced in dogs with autologous blood clot. The experimental animals were divided into 3 groups, that is control group, Ketanserin injection group and PEEP application group. Results: Thirty minutes after embolization, mean pulmonary arterial pressure and pulmonary vascular resistance increased and cardiac output decreased. $PaO_2,\;P\bar{v}O_2$ and oxygen transport decreased and physiological shunt and $PaCO_2$ increased. After injection of Ketanserin, comparing with control group, mean pulmonary arterial pressure, pulmonary vascular resistance and physiological shunt decreased, while cardiac output, $PaO_2$ and oxygen transport increased. All these changes sustained till 4 hours after embolization. After PEEP application pulmonary vascular resistance, $PaO_2$ and $PaCO_2$ increased, while physiological shunt, cardiac output and oxygen transport decreased. After discontinuation of PEEP, mean pulmonary arterial pressure and pulmonary vascular resistance decreased and were lower than control group, while $PaO_2$ and cardiac output increased and higher than control group. $PaCO_2$ decreased but showed no significant difference comparing with control group. Conclusion: It can be concluded that Ketanserin is effective for the treatment of acute pulmonary embolism. With PEEP hemodynamic status deteriorated, but improved better than control group after discontinuation of PEEP. Thus PEEP may be applied carefully for short period in acute pulmonary embolism if the hemodynamic status is tolerable.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.141-145
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• 1999

Purpose : Granisetron is a potent, the most selective 5-HT3 receptor antagonist and is reported to b effective in treatment of radiation-induced emesis. The antiemetic efficacy and safety of oral granisteron was evaluated in patients with receiving highly emetogenic treatment by conventional fractionated irradiation. Materials and Methods : Patients with various cancers who were being treated with irradiation were accrued into the present study. The intensity of nausea was evaluated on first 24 hours and on day-7 by patients according to the degree of interference with normal daily life as followings; a) none; b) present but no interference with normal daily life (mild): c) interference with normal daily life (moderate): and d) bedridden because of nausea (severe). Non or mild state was considered to indicate successful treatment. The efficacy of antiemetic treatment was graded as follows; a) complete response; no vomiting, no worse than mild nausea and receive no rescue antiemetic therapy over the 24h period, b) major response; either one episode of vomiting or moderate/severe nausea or had received rescue medication over 24h period, or any combination of these, c) minor response; two to four episodes of vomiting over the 24h period, regardless of nausea and rescue medication, d) failure; more than four medication. The score of the most symptom was recorded and the total score over 24 hours was summarized. The complete or major response was considered to indicate successful treatment. Results : A total of 10 patients were enrolled into this study, and all were assessable for efficacy analysis. Total nausea control was achieved in 90$\%$ (9/10:none=60$\%$ plus mild=30$\%$) of total patients after 7 days. The control of vomiting by granisteron was noted in seven patients (70$\%$) of complete response and three (30$\%$) of major response with a hundred-percent successful treatment over 7 days. The minor response or treatment failure were not observed. No significant adverse events or toxicities from granisetron were recorded in patient receiving granisetron. Conclusion : We concluded that granisetron is a highly effective antiemetic agent in controlling radiotherapy-induced nausea or vomiting with a minimal toxicity profile.