• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.233-233
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• 1994

인삼 성분이 학습 및 기억력 중진에 미치는 효과를 연구하기 위하여, 학습 및 기억력 저하를 유발하는 약물들에 대한 아답타겐 (상품명) 과 인삼 수 엑기스산의 효과를 관찰하였다. Ethylcholine aziridium ion(AF64A), scopolamine 및 morphine을 쥐 및 생쥐의 해마와 복강에 각 각 주입하여 학습 및 기억력 저하를 유발한 후 아답타겐을 경구 투여하여 학습 및 기억력에 미치는 효과를 수로시험을 통하여 측정하였다. 또한 인삼 수 엑기스산을 일주일 동안 복강 주사하여 각 효과를 수로시험을 통하여 측정하였다. 또한 인삼 수 엑기스산을 일주일동안 복강 주사하여 각종 신경계에 미치는 변화를 효소 활성도, 신경전달물질의 농도, 수용체 결합을 지표로 하여 살펴보았다. AF64A 투여군 중 플랫폼을 전혀 인지치 못한 군에 아답타겐을 투여시에는 투여 횟수에 따라 플랫폼을 인지하는 비율이 증가했다. 연습 후 일주일간 물을 투여한 대조군의 도달 시간에 큰 변화가 없음에 반해, 아답타겐을 투여시에는 3일 투여 후 최대 시간이 걸리고, 투여횟수가 증가할수록 점차 도달 시간이 단축되었다. 인공 뇌척수액 및 AF64A의 투여군에서 아답타겐을 5일간 투여한 경우 대조군보다 각각 3배 빠른 속도로 플랫폼을 기억하였다. 한편 scopola mine 투여시에는 아답타겐을 투여한 군이 투여하지 않은 군보다 약 3배 빨리 플랫폼에 도달하였으나 각 투여군의 매일의 도달 시간 차이에는 변화를 나타내지 않았다. 또한 4일 전에 아답타겐을 투여시에는 saline 및 merphine 투여시 약 1.4배 빨리 플랫폼을 인지하였다. 인삼 추출물을 7일 투여 했을 경우 선조체에서 도파민 합성 효소인 tyrosine hydroxylase 활성이 유의성 있게 증가했으며, 대사체인 DOPAC의 농도도 증가를 나타냈다. 그러나, 도파민, HVA및 대사율인 DOPAC/DA와 HVA/DA에는 변화를 보이지 않았다. 또한 선조체의 GABA농도는 약 66%로 낮아졌지만 AChE의 활성도는 변화가 없었다. 인삼 수 추출물을 2주일 투여시 선조체의 도파민 수용체의 특성변화는, D1 수용체의 친화력에는 변화가 없는 반면, 최대 결합 수용체 수는 약간 낮아졌고, D2 수용체의 경우 최대 결합 수용체수는 변화가 없었으나 친화력은 감소하였다. 또한 피질의 benzodiazipine수용체 결합 친화력에는 변화가 없는 반면 최대 결합 수용체 수는 약 15%의 증가를 나타내었고 연수의 benzodiazepine 및 피질의 GABA 수용체의 특성에는 에는 변화를 나타내지 않았다. 이상의 결과, AF64A, 아급성 scopolamine 및 급성 morphine꽈 투여로 학습능이 저하되고 아답타겐을 경구 투여시엔 저하된 학습능력 빛 기억력의 증가를 보였다. 또한 본 결과는 인삼성분 중에는 도파민 및 GABA신경계에 영향을 주는 성분이 있음을 제시하였다.

• Journal of the korean academy of Pediatric Dentistry
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• v.25 no.4
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• pp.811-824
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• 1998

The purpose of this study was to compare the clinical sedation effect of chloral hydrate and hydroxyzine combination, midazolam, triazolam when young children were sedated for dental treatment. The uncooperative 22 children aged, 25 to 52 months of age(ASA class I) and weighting between 11 and 17kg, participated in the study. Each patient was assigned randomly to receive chloral hydrate(50mg/kg) and hydroxyzine HCl(25mg), midazolam(0.5mg/kg), and triazolam(0.25mg) oral administration : alternative regimens were administered at next appointment. According to rating scale, sleep, crying, movement, and overall behavior response were checked for evaluation of the clinical sedation effect. Pulse rate and oxygen saturation were also measured for monitoring the patients during treatment period by pulse oximeter. The results were as follows: 1. In the evaluation of sedation effect, 90.9% in chloral hydrate and hydroxyzine combination and midazolam, and 77.3% in triazolam were rated "good" or "very good". 2. Sleep was demonstrated to be statistically significant increase in chloral hydrate and hydroxyzine combination group. Despite the fact that chloral hydrate and hydroxyzine group was in a deeper state of sleep, all the children were easily aroused. 3. There were no statistically significance among the three regimens with regard to cry ing, movement, overall behavior. 4. The adverse side effect was vomiting in one patient of chloral hydrate and hydroxyzine combination. There were no clinical sign of respiratory depression.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3759-3765
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• 2015

Background: Approaches in disruption of MDM2-p53 interactions have now emerged as an important therapeutic strategy in resurrecting wild type p53 functional status. The present study highlights virtual screening strategies in identification of high affinity small molecule non-peptidic inhibitors. Nutlin3A and RG7112 belonging to compound class of Cis-imidazoline, MI219 of Spiro-oxindole class and Benzodiazepine derived TDP 665759 served as query small molecules for similarity search with a threshold of 95%. The query molecules and the similar molecules corresponding to each query were docked at the transactivation binding cleft of MDM2 protein. Aided by MolDock algorithm, high affinity compound against MDM2 was retrieved. Patch Dock supervised Protein-Protein interactions were established between MDM2 and ligand (query and similar) bound and free states of p53. Compounds with PubCid 68870345, 77819398, 71132874, and 11952782 respectively structurally similar to Nutlin3A, RG7112, Mi219 and TDP 665759 demonstrated higher affinity to MDM2 in comparison to their parent compounds. Evident from the protein-protein interaction studies, all the similar compounds except for 77819398 (similar to RG 7112) showed appreciable inhibitory potential. Of particular relevance, compound 68870345 akin to Nutlin 3A had highest inhibitory potential that respectively showed 1.3, 1.2, 1.16 and 1.26 folds higher inhibitory potential than Nutilin 3A, MI 219, RG 7112 and TDP 1665759. Compound 68870345 was further mapped for structure based pharamacophoric features. In the study, we report Cis-imidazoline derivative compound; Pubcid: 68870345 to have highest inhibitory potential in blocking MDM2-p53 interactions hitherto discovered.

• Journal of The Korean Dental Society of Anesthesiology
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• v.2 no.1 s.2
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• pp.1-6
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• 2002

The usage of nitrous oxide is increased for the anxious patient to dental treatment. There are two methods to induce the sedation during dental treatment. One is sedation with drugs the other no need of drugs. We discussed here about sedation with drugs. The methods of drug administration are oral, intramuscular, intravenous, inhalation. The method of oral administration of drugs are convenient to patient and doctor but poor controllability. Intramuscular method is a parenteral technique that maintains several advantages over the enteral technique. However its pales in comparison to other parenteral technique. Intravenous method represents most effective method of ensuring predictable and adequate sedation in all patients. But it has inability to reverse the action of drugs after they have been injected except some drugs (e.g., narcotics and benzodiazepine). A variety of gaseous agents may be administered by inhalation to produce sedation. In dental practice, the inhalation administration of gas means use of nitrous oxide. There are many advantages of nitrous oxide administration. First, very short latent period and rapid onset of drug action which lead to possible titration of drug concentration. With nitrous oxide, clinical effects may become noticeable as quickly as 15 to 30 seconds after inhalation. Recovery from inhalation sedation is also quite rapid. In out patient dental practice rapid recovery is very important because it permit to discharge the patient without escort and the patient return to their ordinary life without limit. To success the conscious sedation with nitrous oxide, the administrator should be keep the mind that always titration of nitrous oxide concentration during induction and treatment. Careful observation need during treatment to prevent oversedation because the adequate nitrous oxide concentration to patients changed by environmental stress. Always begins with 100% oxygen and ends with 100% oxygen to prevent diffusion hypoxia which rare in clinical practice.

• Sleep Medicine and Psychophysiology
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• v.12 no.2
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• pp.139-143
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• 2005

Periodic limb movements in sleep (PLMS) have been diagnosed easily by nocturnal polysomnography (NPSG) and treated effectively with dopamine receptor agonist, benzodiazepine and opioid. However, few reports have objectively assessed the treatment responses. We treated a PLMS patient with clonazepam and pramipexole, and evaluated their efficacy with actigraphy. Clonazepam improved sleep quality without reducing frequency of limb movements, and pramipexole reduced frequency of limb movements without improving sleep quality, results which are consistent with previous study findings. Actigraphy proved useful in evaluation of treatment response of PLMS.

• Korean Journal of Biological Psychiatry
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• v.21 no.2
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• pp.49-56
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• 2014

Objectives Previous literature on the prescription change among patients with schizophrenia mainly focused on antipsychotics. This study investigated chronological change in the patterns of discharge medication among inpatients with schizophrenia at a psychiatric inpatient unit of a university-affiliated hospital. Methods All admission records at a psychiatric unit of Hanyang University Guri Hospital with discharge diagnosis of schizophrenia during two different five-year time frames (1996-2000 and 2006-2010) were reviewed including the demographic and clinical data and discharge medications. The data were gathered from a total of 207 patients (95 in 1990s and 112 in 2000s). Results The frequency in use of atypical antipsychotics (p < 0.01), antidepressants (p < 0.05), beta-blockers (p < 0.01), and benzodiazepine (p < 0.01) was significantly higher in 2000s. Anticholinergic drugs were less likely used in 2000s (p < 0.01). We did not find significant differences in the equivalent dose of antipsychotic drugs, the use of mood stabilizers and cholinergic drugs between two time frames. Conclusions Increased proportion of atypical antipsychotics and decreased use of anti-parkinsonian drugs are in line with literature. Our results show that more diverse classes of psychotic medications are used for schizophrenia in recent years. It is likely that psychiatrists are becoming more conscious of negative symptoms, anxiety, and depression in the pharmacotherapy of schizophrenia as well as positive symptoms of the illness.

• 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.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.479-485
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• 2015

This study was performed to investigate the sedative-hypnotic activity of ${\gamma}$-aminobutyric acid (GABA)-enriched fermented marine organisms (FMO), including sea tangle (FST) and oyster (FO) by Lactobacillus brevis BJ20 (L. brevis BJ20). FST and FO were tested for their binding activity of the $GABA_A$-benzodiazepine and 5-$HT_{2C}$ receptors, which are well-known molecular targets for sleep aids. We also measured the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of FST and FO. In $GABA_A$ and 5-$HT_{2C}$ receptor binding assays, FST displayed an effective concentration-dependent binding affinity to $GABA_A$ receptor, similar to the binding affinity to 5-$HT_{2C}$ receptor. FO exhibited higher affinity to 5-$HT_{2C}$ receptor, compared with the $GABA_A$ receptor. The oral administration of FST and FO produced a dose-dependent decrease in sleep latency and increase in sleep duration in pentobarbital-induced hypnosis. The data demonstrate that FST and FO possess sedativehypnotic activity possibly by modulating $GABA_A$ and 5-$HT_{2C}$ receptors. We propose that FST and FO might be effective agents for 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 The Korean Society of Clinical Toxicology
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• v.11 no.1
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• pp.23-27
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• 2013

Zoletil is a non-opioid, non-barbiturate animal anesthetic and proprietary combination of two drugs, a dissociative anesthetic drug, tiletamine, with the benzodiazepine anxiolytic drug, zolazepam. Zoletil has greater potency than ketamine. Zoletil is abused for recreational purposes, especially by people with easy access to medicine. However, in Korea, it is available over-the-counter. Here we report on a case of an 83-year-old woman who received injection of seven vials of "Zoletil 50" by her daughter and presented with an altered mental change. Her mental state was stupor and vital sign was hypotension, bradycardia. Her blood tests indicated metabolic and respiratory acidosis and hyperkalemia. She was treated with intravenous naloxone and flumazenil but was not responsive. She was admitted to the ICU and treated with supportive therapy. Her mental state showed transient recovery, however, her clinical manifestation worsened and she expired.