• YAKHAK HOEJI
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• v.49 no.5
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• pp.437-442
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• 2005

The purpose of this study was to characterize the putative anxiolytic-like effects of phenylpropanoids using the elevated plus maze (EPM) test in mice. Cinnamic acid, p-coumaric acid, caffeic acid and ferulic acid were orally administered to male ICR mice, 1 h before behavioral evaluation in an EPM, respectively. Control mice were treated with an equal volume of vehicle, and positive control mice diazepam (1 mg/kg). A single treatment with phenylpropanoids (at 8 mg/kg) significantly increased time-spent and arm entries into the open arms of the EPM, and decreased time-spent and arm entries into the closed arms of the EPM versus control (P<0.05). However, no changes in the locomotor activity and myorelaxant effect were seen in any group versus the saline control. These results suggest that phenylpropanoids may be an effective anx-iolytic agent.

• Korean Journal of Clinical Pharmacy
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• v.15 no.2
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• pp.149-159
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• 2005

Purpose: To determine the extent and rate of prescription drug therapy, especially polypharmacy and the prevalence of potentially inappropriate medication use in Korean elderly ambulatory patients based on an explicit criterion. Methods: Performed a retrospective study of 65 years or older ambulatory patients visiting a university hospital based clinic from January 2002 to April 2004. Study determined the patterns of drug prescription per Anatomical Therapeutic Chemical Classification and the potentially inappropriate medication usage based on explicit Beers criteria. Results: Of the 4,042 elderly patients the mean number of prescription was $2.2{\pm}2.0$, which was similar between genders and all age groups within the elderly. 10.7% of patients were prescribed with more than 5 medications concurrently. The most frequently prescribed medication was the drugs used for treating nervous system diseases (44.3%), followed by alimentary tract/metabolism disorders (27.6%), cardiovascular disease (10.7%), blood/blood forming disorders (4.3%), respiratory disorders (6.5%), and musculoskeletal diseases (3.2%). A total of 511 elderly (13%) was prescribed with medication that met the criteria for=1 potentially inappropriate drugs for the elderly. This proportion was similar between genders and all age groups within the elderly. Among these 511 elderly patients the mean number of potentially inappropriate drugs prescribed was $5.1{\pm}3.3$ drugs. Potentially inappropriately prescribed drugs included amitriptyline (76 cases), diazepam (69 cases), ketorolac (57 cases), short acting nifedipine (44 cases), triazolam (38 cases), and hydroxyzine (38 cases). Conclusion: Potentially inappropriate drug prescribing in Korean ambulatory elderly patients are common. Education programs and interventions aimed at optimizing the prescribing and dispensing of the most appropriate drugs are needed.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.586-592
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• 2017

Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via ${\gamma}$-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice. Oral administration of SIN (40 mg/kg) markedly reduced spontaneous locomotor activity, similar to diazepam (a benzodiazepine agonist) in mice. SIN shortened sleep latency, and increased total sleep time in a dose-dependent manner when co-administrated with pentobarbital (42 mg/kg, i.p.). SIN also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). SIN reduced the number of sleep-wake cycles, and increased total sleep time and non-rapid eye movement (NREM) sleep. In addition, SIN also increased chloride influx in the primary cultured hypothalamic neuronal cells. Furthermore, protein overexpression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through $GABA_A$-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.119-142
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• 2008

Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of anxiety and insomnia in Korea and China. This experiment was performed to know whether sanjoinine A, one of major alkaloid compounds of ZSS has anxiolytic and hypnotic effects through the GABAergic systems. Our results showed that administration of sanjoinine A increased open arm entries and spent time in open arm in the elevated plus-maze and increased head dips in hole board test. Different from traditional anxiolytic, diazepam, sanjoinine A itself did not decrease locomotor activity and strength level in mice. Furthermore, Sanjoinine A (0.5-2.0 mg/kg) prolonged sleeping time and reduced sleeping latency induced by pentobarbital in a dose-dependent manner similar to muscimol, a $GABA_A$ receptor agonist. Sanjoinine A (0.25-1.0 mg/kg) also increased sleeping rate and sleeping time in the combined administration at the sub-hypnotic dose of pentobarbital and showed synergic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by pentobarbital. However, sanjoinine A itself did not induce sleeping at the higher dose. In addition, both of sanjoinine A and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A decreased the $GABA_A$ receptor ${\alpha}$-subunit expression and increased ${\gamma}$-subunit expression, and had no effects on abundance of ${\beta}$-subunit in primary cultured cerebellar granule cells, showing different expression of subunits from pentobarbital. In conclusion, sanjoinine A shows anxiolytic-like effects and augments pentabarbital-induced sleeping behaviors through the modification of GABAergic systems. [This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (The Regional Research Universities Program/Center for Healthcare Technology Development)].

• Journal of Veterinary Clinics
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• v.14 no.2
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• pp.244-253
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• 1997

This study was performed to evaluate the possibility of inducing analgesia by electroacupuncture stimulation at single acupoint or combined acupoints and to examine the analgesic effects following the combination of premedication and electroacupunrture analgesia(EA). Analgesia was induced by EA with the current of 1-4 volts and the frequency of 10-45 Hz to the acupoints Uown to be related to analgesia on the head/necIL axial part thoracic and pelvic limb. In Yi Feng acupoint of head/neck part pain responses were not disappeared after electroacupunrture stimulation to the head/necIL thoracic limbo thoraxl abdomen, loin, rear and pelvic limb. Pain responses were remained after EA of Tian Men-Tian Ping and Shen Yu arupoints of axial park whereas hypoalgesia was observed after EA of Tian Ping-Bai Hui acupoint in all parts of body. There was no analgesic effects after EA stimulation of the brachial plexus and Wai Kuan acupoint, whereas after EA stimulation of San Yang Lo, pain responses were disappeared in headfnecll, thoracic limb and pelvic limbo and in the other parts of body hypoalgesia was shown. In EA stimulation of Tsu San Li acupoint pain responses were disappeared in pelvic limb and in San Yin Chiao acupoint pain responses were disappeared in head/necIL thoracic and pelvic limb, and hypoalgesia was shown in abdomen. On the combination of San Yang Lo Pli Men) and San Yin Chiao (Pu Yan6 acupoints, pain response in heauneck was decreased in 5 minutes, whereas analgesia in thoracic and pelvic limb was induced after 20-30 minutes and in abdomen was noted after 50 minutes. The more frequrncy was increased, the more rapid analgesic e11%t was induced. The analgesic effects wert not good in laparotomy under EA at the combination of San Yang Lo (Xi Men) and San Yin Chiao (Pu Yang) arufoints. Enteroanastomosis could not be continued under acrpromazine, xylazine and diazepam with EA. However, under EA followed by tiletaminetzolazepam, the operation could be completed without additional anesthesia and the analgesic effects were good. There were no changes in clinical signs, hematological and serological values after combination of the premeditation of tiletamine+zolaEepam and EA. It is considered that EA alone is not suitable for the main surgery, but the combination method of EA and sedatives can be utilized in practice.

• YAKHAK HOEJI
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• v.36 no.5
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• pp.496-505
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• 1992

The correlation between GABA receptors($GABA_A$ and $GABA_B$ receptor) and benzodiazepine receptor on the saline infusion-induced micturition reflex contraction was studied in the female rat. To investigate the effect of ${\gamma}-aminobutyric$ acid(GABA) on the micturition reflex, exogenous GABA(10 mg/kg) and GABA transaminase inhibitor(aminooxyacetic acid; AOAA $1\;{\mu}g$) were administered intravenously(i.v.) and intracerebroventriculary(i.c.v.), respectively. In result, both GABA and AOAA inhibited the saline induced micturition reflex contraction. This AOAA induced inhibition of micturition reflex was blocked by both bicuculine. $GABA_A$ receptor antagonist, and Ro 15-1788, benzodiazepine receptor antagonist. Muscimol, $GABA_A$ receptor antagonist($0.1\;{\mu}g$ i.c.v., $3\;{\mu}g$ intrathecal; i.t., 1 mg/kg i.v.) and baclofen, $GABA_A$ receptor agonist($1\;{\mu}g$ i.c.v., $3\;{\mu}g$ i.t., 1 mg/kg i.v.) also inhibited the bladder contraction. Pretreatment of bicuculline($1\;{\mu}g$ i.c.v.), but not of 5-aminovaleric acid(AVA, $1\;{\mu}g$ i.c.v.), $GABA_B$ receptor antagonist blocked the central inhibition of muscimol. These inhibitory effects were reversed by Ro15-1788 but were potentiated by flurazepam, benzodiazepine receptor antagonist. On the other hand, the inhibitory effects of baclofen were not affected by Ro 15-1788. Diazepam and flurazepam also inhibited the micturition reflex contraction when they were administered $3\;{\mu}g$ i.c.v., $10\;{\mu}g$ i.t., $10\;{\mu}M$, $30\;{\mu}M$ transurethrally, respectively. In conclusion, these results suggest that the micturition reflex is mediated by $GABA_A$, $GABA_B$ receptor and benzodiazepine receptor. The bezodiazepines increase the receptor binding of GABA to the $GABA_A$ receptor, so that the benzodiiazepines show the synergistic effect on the inhibition of the micturition reflex contraction, but not to the $GABA_B$ receptor.

• Annals of Clinical Neurophysiology
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• v.5 no.2
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• pp.171-176
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• 2003

Backgrounds and Objectives: Despite of enormous clinical and laboratory researches focused on the useful markers in status epilepticus(SE), clinically applicable methods are not yet available. Although ketogenic diet (KD) is an old method of treating epilepsies, its outstanding antiepileptic effect in some epileptic patients needs re-evaluation of this methods. This study was performed to evaluate the effect of KD on the change of nitric oxide(NO) during the SE. Methods: After the determination of critical EEG stages in the pilocarpine-induced SE model, serum NO levels were measured with Griess reaction. Open cardiac puncture was done immediately after the four different EEG stages of SE in the KD rats and regular diet (RD) rats. Cessation of SE was done with the 10~20 mg/Kg of diazepam i.p. injection in each stages of SE in KD and RD rats. Results: Pilocarpine-induced SE showed reliable EEG and behavioral patterns in all rats. Also, KD did not affect the SE induced by pilocarpine in terms of the SE induction time and SE severity. Serum NO was consistently higher in KD rats than RD rats in all SE stages. Conclusions: KD significantly increases NO during the pilocarpine-induced SE. These finding might contribute the neuroprotective effect of KD in the SE.

• YAKHAK HOEJI
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• v.57 no.2
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• pp.101-109
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• 2013

Depressive disorders are the most common psychiatric problem in the elderly. Most depression treatment guidelines emphasize treatment with antidepressant medication and recommend that benzodiazepine use be minimized for limited period, particularly to elderly patients. In order to evaluate appropriate use of antidepressants and benzodiazepine, retrospective review of prescriptions was performed. The study population are older than 65 years who had been newly diagnosed with major depressive disorder in specialty mental health at a community general hospital from January $1^{st}$, 2007 to October $31^{th}$, 2012 (N=373). Initial antidepressant accounted for 89.5% with SSRI, and escitalopram accounted for 60.9% of SSRI group. 79% or more of the patients were prescribed the recommended dosage. The maintenance rate for 4 weeks of initial antidepressant was 48% and 6 weeks was 39%. Treatment-discontinuation rate was 68% at 3 month. Alprazolam (short acting benzodiazepine) was prescribed the most, followed by clonazepam (long acting benzodiazepine) and then diazepam. 55% of patients received a duplicated prescription for short acting plus long acting benzodiazepine. 61% of patients used long acting benzodiazepines. Prescribed dosages of benzodiazepines were commonly within a recommended range, while no one was prescribed a appropriate period (up to 2 weeks) except for the early discontinued patients. Appropriate use of zolpidem was only 16.2%. The depressed elderly treated in specialty mental health mostly received long-term treatment with benzodiazepines in combination with antidepressants, guideline recommendations was not followed. Multidisciplinary interventions like audit and feedback of benzodiazepine use are needed and education for the elderly is needed to properly maintain antidepressant treatment.

• Journal of Veterinary Clinics
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• v.38 no.4
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• pp.204-209
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• 2021

A seven-month-old castrated male Chihuahua weighing 1.6 kg presented with generalized tonic-clonic seizure following ingestion of isoniazid. Emergency treatment with three doses of diazepam (total 1.5 mg/kg, intravenous [IV]) and phenobarbital (15 mg/kg IV) was administered. The seizure stopped after administration of propofol (constant rate infusion [CRI]; 0.2 mg/kg/min). Blood analyses showed mildly increased serum blood glucose concentration, hyperkalemia, and hyperphosphatemia. On suspicion of isoniazid toxicity, activated charcoal (1 g/kg, orally), lipid emulsion (CRI; 9 mL/hr), and pyridoxine hydrochloride (70 mg/kg IV) were added to the treatment regimen. Twelve hours after presentation, the dog showed increased serum liver enzyme activities, serum blood urea nitrogen, and creatinine concentrations indicating hepatic and renal failure. Twenty-two hours after presentation, blood analysis still revealed increased liver enzyme activities, blood urea nitrogen, and creatinine concentrations with low blood glucose concentration. Twenty-six hours after presentation, the dog's vital signs deteriorated and the owner elected for the dog to be euthanized. This is the first report of the clinical course of isoniazid toxicosis in a dog in South Korea. Furthermore, to our best knowledge, this is the first report where secondary multiple organ failure was observed due to isoniazid toxicosis. Clinicians should be aware of the possibility of isoniazid toxicosis in dogs. Rapid initiation of treatment after clinical recognition is warranted in such cases.

• CELLMED
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• v.11 no.3
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• pp.14.1-14.9
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• 2021

Background: Cuscuta reflexa Roxb is a member of the Cuscutaceae family, and in Unani medicine, it is known as Aftimoon. It is a parasitic plant that can be found growing abundantly on various host plants in India up to 3000 metres in altitude during the rainy season. Unani physicians have been using it for years to cure a variety of illnesses, including psychiatric illnesses like melancholia, schizophrenia, and epilepsy. It has been used to cure hepatitis, palpitations, and skin disorders, among other things. Objective of the study: To evaluate anti-anxiety effect of Cuscuta reflexa Roxb in Swiss Albino mice of either sex. Materials and Methods: A total of 24 Swiss Albino mice weighing 25-35 g were used in this study. Animals were chosen at random and held in their cages for at least 7 days in a standard setting. Group A was given regular saline as a vehicle, Group B was given a hydro alcoholic extract of the lower dose of the test drug, Group C was given a hydro alcoholic extract of the higher dose of the test drug, and Group D was given the standard drug Diazepam 5 mg/kg orally. Aftimoon as hydro alcoholic extract (200 mg/kg and 400 mg/kg body wt.) was given in single and double doses and observed for 7 days. Results: For each parameter in each category, mean and standard deviations were computed. For multiple group comparisons, a one-way ANOVA was used, followed by Turkey's post hoc test. (p<0.05) was used as the significance standard. Conclusion: These results advocate that the Aftimoon as double dose (400 mg/kg body wt.) revealed anti-anxiety effect similar to standard drug.