• 약학회지
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• 제48권5호
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• pp.278-284
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• 2004

In order to determine the bioavailability of c1onazepam, an anxiolytic drug, a simple, rapid and sensitive HPLC analysis was developed in healthy Korean volunteers. The analysis system was validated in specificity, accuracy, precision and linearity. The analysis condition we established was 2.58 min and 5 ng/$m\ell$ in retention time and limit of quantitation of c1onazepam, respectively, using reverse-phase C18 column connected to UV detector. Quantitation was performed at 235 nm wave length with p-hydroxybenzoic acid ethyl ester as internal standard. The method involved a simple extraction. In order to study blood level profiles as a function of time, eight volunteers were enrolled and orally took 6 mg clonazepam once. The blood samples were collected from 0 to 120 h after the drug administration. Mean AUC and Cmax value were 1028.17$\pm$568.165 (ng/$m\ell$$.$hr) and 41.25$\pm$10.82 (ng/$m\ell$), respectively. And mean Tmax and T$_{1}$2/ value were 1.08$\pm$0.42 (hr) and 30.78$\pm$3.26 (hr). From the results we determine the pharmacokinetic characteristics of clonazepam in Korean people using a newly developed and useful HPLC method.

• Natural Product Sciences
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• 제27권3호
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• pp.141-150
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• 2021

This short review on the chemistry, pharmacological properties and patents of obovatol and obovatal from Magnolia obovata is the first publication. Pharmacological properties are focused on anti-cancer, anti-inflammatory, anti-platelet and neuroprotective activities. Obovatol and obovatal were first isolated from the leaves of M. obovata. Also reported in the bark and fruits of M. obovata, obovatol and obovatal are neolignans i.e., biphenolic compounds bearing a C-O coupling. Other classes of compounds isolated and identified from M. obovata include sesquiterpene-neolignans, dineolignans, trineolignan, lignans, dilignans, phenylpropanoids, phenylethanoid glycosides, flavonoids, phenolic acids, alkaloids, sesquiterpenes, ketone and sterols. The anti-cancer properties of obovatol and obovatal involve apoptosis, inhibition of the growth, migration and invasion of cancer cell lines. However, obovatol displays cytotoxicity against cancer cells but not obovatal. Similarly, anti-inflammatory, anti-platelet, neuroprotective, anxiolytic and other pharmacological activities were only observed in obovatol. The disparity in pharmacological properties of obovatol and obovatal may be attributed to the -CHO group present in obovatal but absent in obovatol. From 2007 to 2013, eight patents were published on obovatol with one mentioning obovatal. They were all published at the U.S. Patent and Trademark Office by scientists of the Korea Research Institute of Bioscience and Biotechnology (KRIBB) as inventors and assignee, respectively. Some future research and prospects are suggested.

• The Korean Journal of Physiology and Pharmacology
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• 제23권1호
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• pp.81-87
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• 2019

Ketamine has long been used as an anesthetic agent. However, ketamine use is associated with numerous side effects, including flashbacks, amnesia, delirium, and aggressive or violent behavior. Ketamine has also been abused as a cocktail with ecstasy, cocaine, and methamphetamine. Several studies have investigated therapeutic applications of ketamine, demonstrating its antidepressant and anxiolytic effects in both humans and rodents. We recently reported that neonatal maternal separation causes enhanced anxiety- and aggressive-like behaviors in adolescent. In the present study, we evaluated how acute and chronic ketamine administration affected the behavioral consequences of neonatal maternal separation in adolescent mice. Litters were separated from dams for 4 hours per day for 19 days beginning after weaning. Upon reaching adolescence (post-natal day 35-49), mice were acutely (single injection) or chronically (7 daily injections) treated with a sub-anesthetic dose (15 mg/kg) of ketamine. At least 1 h after administration of ketamine, mice were subjected to open-field, elevated-plus maze, and resident-intruder tests. We found that acute ketamine treatment reduced locomotor activity. In contrast, chronic ketamine treatment decreased anxiety, as evidenced by increased time spent on open arms in the elevated-plus maze, and remarkably reduced the number and duration of attacks. In conclusion, the present study suggests that ketamine has potential for the treatment of anxiety and aggressive or violent behaviors.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제45권3호
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• pp.152-157
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• 2019

Objectives: The number of elderly patients with systemic basal disease requiring invasive dental treatment has increased. Appropriate prediction of surgical invasiveness and combined use of psychosedation are thought to contribute to safe whole-body management. Dexmedetomidine (DEX) exhibits analgesic and anti-anxiolytic properties and causes mild respiratory depression. Studies regarding DEX use in elderly non-intubated patients are scarce. We aimed to use retrospective data to determine an effective dose of DEX to induce adequate sedation in elderly patients undergoing invasive dental surgery under local anesthesia. Materials and Methods: One hundred two patients aged 70 to 96 years were presumably appropriately controlled with sedation. DEX was administered at an initial loading dose of 2.0 to $3.1{\mu}g/kg/hr$ for 10 minutes. We divided the patients into five groups by age and compared their blood pressures and heart rates. Results: In all five groups, blood pressure decreased suddenly at approximately 15 and 20 minutes after DEX administration. A marked decrease in blood pressure was noted in patients aged 75 to 79 years. Conclusion: For elderly patients aged 75 years and above, the initial loading dose of DEX needs to be reduced to lower than half that required for young and middle-age adults.

• 한국약용작물학회지
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• 제14권2호
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• pp.70-76
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• 2006

Paeoniae radix has been widely used for its anti-allergic, anti-inflammatory and analgesic effects, and demonstrated to have anticonvulsant, memory enhancing and anxiolytic activities. The present study was performed to examine the protective effect of methanol extract of Paeoniae radix (PR) from Paeoniae Japonica Miyabe et Takeda (Paeoniaceae) on hydrogen peroxide $(H_2O_2)-induced$ neurotoxicity using cultured rat cerebral cortical neuron. $H_2O_2$ produced a concentration-dependent reduction of neuronal viability, PR, over a concentration range of 10 to $100\;{\mu}g/ml$ showed concentration-dependent decrease of the $H_2O_2$$(100\;{\mu}M)-induced$ neuronal cell death, as assessed by a 3-[4,5-dimethylthiazol-2-yl]-2,5-di-phenyl-tetrazolium bromide assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. PR $(100\;{\mu}g/ml$ inhibited $100\;{\mu}M$ $H_2O_2-induced$ elevation of the cytosolic $Ca^{2+}$ concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, flue-4 AM. PR $(50\;{\mu}g/ml$ inhibited glutamate release into medium induced by $100\;{\mu}M$ $H_2O_2$, which was measured by HPLC, and generation of reactive oxygen species (ROS). These results suggest that PR may mitigate the $H_2O_2-induced$ neurotoxiciy by interfering with the increase of $[Ca^{2+}]_c$, and then inhibiting glutamate release and generation of ROS in cultured neurons.

• 동의신경정신과학회지
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• 제22권2호
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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.

• 동의신경정신과학회지
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• 제25권3호
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• pp.297-310
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• 2014

Objectives: This study is designed to investigate the effects of Banhahubak-Tang Extract (BHTe) on stress. Methos: BHTe was fed to ICR male mice ($20{\pm}2g$) orally with the dose of 100 mg/kg/day for five days. Mice were then exposed to sociopsychological stress by observing foot shock stressed mice for one hour for five days while restrained. Results: 1) The BHTe-administered group showed a tendency of decreasing of serum corticosterone secretion compared with the control group. 2) The BHTe-administered group showed an increase in noradrenalin secretions in the dorsal cortex of the brain, but it was not significant. 3) BHTe administration had no effect on the brain level of lipid peroxidation. 4) BHTe administration decreased the serum level of lipid peroxidation. 5) BHTe administration decreased the Cu,Zn-SOD in the brain. 6) BHTe administration had no effect on catalase activity in the brain. 7) BHTe administration had no effect on the brain level of GSH. 8) BHTe administration increased the serum level of DPPH free radical scavenging activity, but not significantly enough to make a comparison with BHT. 9) The elevated plus-maze test is designed to detect the effect of anxiolytic drugs. The BHTe group showed a significant increase in latency time. Conclusions: These results suggest that BHTe can effectively rid the subject of the effects of sociopsychological stress.

• 대한약리학회지
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• 제28권1호
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• pp.19-25
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• 1992

Nonbenzodiazepine계 항불안제인 buspirone을 이용하여 건강한 8명의 남자를 대상으로 prolactin과 cortisol분비를 측정하였다. Buspirone는 $Dopamine_2$ 수용체 antagonist 성질 뿐 아니라 $5-HT_{1A}$ partial agonist 효과가 있는 것으로 보고되고 있다. Buspirone 30mg 경구투여시 혈청 prolactin 농도는 유의한 증가를 보였으나 혈청 cortisol 농도의 변화는 차이가 없었다. beta adrenoreceptor antagonist이면서 $5-HT_{1A}$ 수용체 antagonist로 알려진 pindolol (30mg)을 경구 투여한 결과 기초 혈청 prolactin이나 cortisol 농도는 유의한 차이가 없었다. Pinodlol을 전처치한 경우 buspirone-induced prolaction 분비의 유의한 억제효과는 없었다. 이상의 성적은 buspirone-induced prolactin 분비증가는 아마도 $5-HT_{1A}$ 수용체 활성과 관련되지 않음을 시사하는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.183-192
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• 2018

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.

• 대한본초학회지
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• 제27권4호
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• pp.81-88
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• 2012

Objective : Banhahubak-tang is indicated for globus hystericus, marked by a subjective sensation as if something stuffed in the throat, chest distress, cough or vomiting, greasy whitish, taut and smooth pulse. In this study, the effects of Banhahubak-Tang extract (BHTe) were tested for anti-stress action. Methods : BHTe was extracted by pure water using electronic extractor and then fed to ICR male mice ($20{\pm}2g$) orally with the dose of 100mg/kg/day for five days. Mice were exposed to sociopsychological stress by restraining and seeing foot shock stressed mice for one hour for five days. Results : BHTe administered group showed a tendency of decreasing of serum corticosterone secretion when compared with control group, and BHTe administration also significantly up-regulated noradrenaline secretions in the dorsal cortex of brain. Lipid peroxidation of the brain tissues of mice were tested by measuring malondialdehyde, but BHTe showed no significant change. The elevated plus-maze test was designed to detect the effect of anxiolytic drugs, and BHTe administered group showed a significant increase of latency time. Conclusions : These results suggest that BHTe can effectively rid the psychological stress and it's related diseases.