• 약학회지
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• 제54권4호
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• pp.300-308
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• 2010

Adrenoceptor has been considered to be an important target in psychiatric disorders. Based on x-ray structures of bovine rhodopsin, we established homology model of ${\alpha}_{2c}$-adrenoceptor (ADA2C_rat) and then analyzed docking from binding model of receptor-ligand complex with high-active compound No.29 in tricyclic isoxazole analogues (1-30). We observed that the N (1.907 $\AA$) and O (1.712 $\AA$) atoms of isoxazole ring on the docked ligand (No.29) formed H-bonding interaction with O-H of Ser5.32 and carmeron phenyl ring centroid of tricyclic isoxazole formed $\pi-\pi$ interaction at 3.342 $\AA$ distance with phenyl ring centroid of Phe6.52. According to predictions of blood-brain distribution (logBB) through penetration of blood-brain barrie (BBB) and polar surface area (PSA) of the ligands, the high-active compound No.29 has values of logBB=-0.203, PSA=67.50, respectively. These results suggest that the high-active compound No.29 is a novel anti-depressant with the characteristics such as dopamine and serotonin.

• 대한약리학회지
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• 제16권1호
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• pp.57-63
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• 1980

The Pharmacologic action of ethanol extracts and essential substance obtained from fruits of Evodia rutaecarpa are studied. 1) Motility of the isolated rabbit-intestine was decreased in proportion to the concentration of essential substance. 2) Intestinal contraction induced by acetylcholine 10? 6g/ml was inhibited by the essential substance $10^{-5}g/ml$. 3) Contractile responses of the isolated rabbit-intestine by serotonin $10^{-5}g/ml$ and histamine $10^{-5}g/ml$ were depressed significantly with the essential substance $10^{-5}g/ml$. 4) Alpha adrenergic receptor blocking effect of dihydroergotamine was interfered significantly with the essential substance. 5) Analgesic effect in mice by acetic acid stimulating method was observed significantly with both of the ethanol extracts and essential substance. 6) Blood pressure and respiration of the rabbits were not significantly influenced with the essential substance.

• Bulletin of the Korean Chemical Society
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• 제33권12호
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• pp.4035-4040
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• 2012

Presented study describes the synthesis of photo cross-linkable and water soluble hydroxyethyl starch hydroxyethyl methacrylate (HESHEMA) samples with different degree of substitution (DS) by functionalization of hydroxyethyl starch (HES) with hydroxyethyl methacrylate (HEMA) or hydroxyethyl methacrylate carbonylimidazole (HEMACI) in DMSO using two different routes. It was revealed that the reaction time for HESHEMA synthesis can be reduced from 5 days to 24 h by conducting the reaction at $80^{\circ}C$ instead of at room temperature. Solubility of HESHEMA was found to be dependent on DS which in turn was dependent on ratio between HES and HEMA or HEMACI. HESHEMA samples with DS > 0.24 depicted insoluble in water, whereas the samples with DS < 0.05 did not form appreciable gel. HESHEMA samples with appropriate DS were converted into hydrogels by cross-linking polymer chains under UV radiations and resulting HESHEMA hydrogels showed swelling up to 1200%. Application of HESHEMA in controlled drug delivery was investigated by diffusion based encapsulation of Ondansetron, a serotonin 5-$HT_3$ receptor antagonist drug, mainly used for nausea and vomiting treatment.

• 한국식품과학회지
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• 제51권1호
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• pp.64-69
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• 2019

Gluten proteins are key to developing a unique quality of flour because they confer viscosity, cohesiveness, and elasticity in the dough. However, gluten can impede digestion and absorption in gluten-sensitive individuals. In this study, enteritis was induced in mice with dextran sulfate sodium (DSS) salt. The mice later received a diet consisting of 3%, 12%, or 30% fermented noodles with degraded gluten (FNDG) or 30% normal noodle flour for 8 weeks. FNDG did not alter the growth performance or body composition. However, FNDG resulted in increased amylase activity in a dose-dependent manner (p<0.001), and it also improved the digestive capacity. FNDG at 30% concentration increased the level of gastrin (p<0.01) implying increased gut motility. The serotonin receptor levels were significantly reduced by FNDG at 12% (p<0.05) and 30% (p<0.01) concentrations. These findings indicate that a diet containing FNDG could help in the recovery from intestinal inflammation with improving digestive ability and gut motility. Overall, the inclusion of degraded gluten in the diet was found to enhance digestion, gut motility, and absorption in mice.

• 대한핵의학회지
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• 제31권1호
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• pp.9-18
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• 1997

목 적 : 본 연구에서는 정량적 자가방사선사진법을 이용하여 비정형 항정신병 약물의 하나인 risperidone 이 백서 뇌의 신경수용체에 어떻게 작용하는지를 알아보고자 하였다. 대상 및 방법 : 급성투여군은 백서 30마리를 6군으로 나누어 0, 0.1, 0.25, 0.5, 1, 2mg/kg의 risperidone을 복강내 투여하고 2시간후에 단두하였고, 만성투여군은 0, 0.1, 1mg/kg의 risperidone을 21일간 복강내 투여후 단두하여 정량적자가 방사선사진법으로 $5-HT_2$과 $D_2$ 수용체에 대한 [$^3H$]spiperone 결합을 측정함으로써, 선조체, 측좌핵, 전두엽피질 각각의 $5-HT_2$과 $D_2$ 수용체의 분포변화를 측정하고 투여량에 따른 수용체의 영향을 ANOVA 검정으로 분석하였다. 결 과 : 급성투여군에서 $5-HT_2$ 수용체는 전두엽 피질에서 risperidone 투여후 0.1-2mg/kg의 투여 범위전체에서 [$^3H$]spiperone 결합이 대조군에 비하여 32% 이하로 감소하여 통계적으로 유의한 차이를 보였으며, 선조체와 측좌핵의 피질하 수용체에서는 거의 결합을 보이지 않았다. $D_2$ 수용체는 risperidone 투여량의 증가에 따라 선조체와 측좌핵의 [$^3H$]spiperone 결합이 감소하였으며, 1-2mg/kg의 투여량을 준 경우에는 대조군에 비해 57% 이하로 감소하여 통계적으로 유의한 차이를 보였다. 만성투여군에서는 피질의 $5-HT_2$ 수용체가 대조군에 비하여 저용량투여군과 고용량투여군에서 각각 51%와 46%로 감소하였다. 결론 : Risperidone은 $D_2$ 수용체를 약하게 차단하며 $D_2$ 수용체에 영향을 주는 양보다 적은 양을 투여해도 $5-HT_2$ 수용체를 차단하는 효과를 보임으로써 $5-HT_2$ 수용체에 강력히 작용하는 비정형 항정신병 약물임을 알 수 있었다.

• 대한수의학회지
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• 제34권3호
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• pp.447-456
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• 1994

In order to elucidate the characterization of receptors involved in inestinal motility of Israeli carp, spontaneously contracting Israeli carp intestinal preperations were prepared and mounted in the organ chambers for contraction traicings using a polygraph. Various contractile agonists were treated and their dose-response curves were constructed. $EC_{50}$ values$(pD_2)$ of each agonist on specific receptors, $pA_2$ values of competitive antagonists against some agonists, and $K_1$, values of noncompetitive antagonists against some agonists were analyzed for characterization of receptors related with the intestinal contraction. Results obtained through the experiments were summarized as follows: 1. Acetylcholine(ACh) exhibited biphasic dose-response curves: initial ACh-induced dose dependent contractions were observed in pM levels but followed by decreased response in in-between concentration levels. Dose dependent contractions reappeared in ${\mu}M$ level. The peaks in pM and ${\mu}M$ levels appeared in $10^{-13}M$ and $3{\times}10^{-5}M$, respectvely. 2. Carbachol(CaCh) exhibited dose dependent contractions from $10^{-9}M$ to $10^{-5}M$, and its $pD_2$ values were higher than those of ACh($5.60{\pm}0.11$). ACh and CaCh exhibited equiactive contractions. Nicotine had no effects on contractile responses of Israeli carp intestine. 3. ACh-induced responses were inhibited by atropine($K_1:7{\times}10^{-8}M$), a muscarinic antagonist, in a non-competitive manner. But CaCh-induced responses were inhibited by both antimuscarinic atropine($pA_2:9.52{\pm}0.14$) and selective $M_2$ antagonistic 4-DAMP($pA_2:8.16{\pm}0.09$), in competitive manners. Nicotine receptor antagonistic decamethonium and hexamethonium had no effects on ACh-and CaCh-induced contractions. Therefore, the cholinergic receptor related to intestinal motility of Israeli carp was assumed as $M_2$ type. 4. In Israeli carp intestine, 5-HT (serotonin) exhibited dose dependent contractions in concentration range from $10^{-8}M$ to $10^{-5}M$. The maximal responses, however, were corresponded to about 50% of those of ACh or CaCh. 5-HT induced contractions were inhibited by $5-HT_2$ antagonistic ketanserin ($K_1: 7.8{\times}10^{-4}M$) in a non-competitive manner, but not by both of anti $5-HT_1$, spiperone and anti $5-HT_3$, MDL-72222. Hence, $5-HT_2$ receptors are suggested to be existed in Isreli carp intestine.

• Archives of Pharmacal Research
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• 제27권10호
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• pp.1065-1072
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• 2004

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

• Journal of Ginseng Research
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• 제39권4호
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• pp.354-364
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• 2015

Background: Intracellular $Ca^{2+}$($[Ca^{2+}]_i$) is a platelet aggregation-inducing molecule. Therefore, understanding the inhibitory mechanism of $[Ca^{2+}]_i$mobilization is very important to evaluate the antiplatelet effect of a substance. This study was carried out to understand the $Ca^{2+}$-antagonistic effect of total saponin from Korean Red Ginseng (KRG-TS). Methods: We investigated the $Ca^{2+}$-antagonistic effect of KRG-TS on cyclic nucleotides-associated phosphorylation of inositol 1,4,5-trisphosphate receptor type I ($IP_3RI$) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in thrombin (0.05 U/mL)-stimulated human platelet aggregation. Results: The inhibition of $[Ca^{2+}]_i$ mobilization by KRG-TS was increased by a PKA inhibitor (Rp-8-BrcAMPS), which was more stronger than the inhibition by a cyclic guanosine monophosphate (cGMP)- dependent protein kinase (PKG) inhibitor (Rp-8-Br-cGMPS). In addition, Rp-8-Br-cAMPS inhibited phosphorylation of PKA catalytic subunit (PKAc) ($Thr^{197}$) by KRG-TS. The phosphorylation of $IP_3RI$ ($Ser^{1756}$) by KRG-TS was very strongly inhibited by Rp-8-Br-cAMPS compared with that by Rp-8-BrcGMPS. These results suggest that the inhibitory effect of $[Ca^{2+}]_i$ mobilization by KRG-TS is more strongly dependent on a cAMP/PKA pathway than a cGMP/PKG pathway. KRG-TS also inhibited the release of adenosine triphosphate and serotonin. In addition, only G-Rg3 of protopanaxadiol in KRG-TS inhibited thrombin-induced platelet aggregation. Conclusion: These results strongly indicate that KRG-TS is a potent beneficial compound that inhibits $[Ca^{2+}]_i$ mobilization in thrombin-platelet interactions, which may result in the prevention of platelet aggregation-mediated thrombotic disease.

• 생물정신의학
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• 제3권1호
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• pp.121-126
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• 1996

최근에 정신분열증의 병태생리에 세로토닌계에 대한 관심이 고조되고 있고 cimetidine이 간접적인 세로토닌계 자극으로 PRL 분비 반응을 유발한다 하여 본 연구에서는 양성 및 음성 증상 척도 (PANSS)에 의하여 양성 및 음성 아형으로 정신분열증 환자군을 구분, 정상대조군과 두 아형들간의 PRL 기저지와 cimetidine 유발성 PRL $T_{30}$치를 측정하여 정신분열증의 아형에 따른 seretonin과의 상관 관계를 규명하고자 연구가 시도되었다. 대상은 DSM-N(APA 1994)의 진단 기준을 만족시키는 입원 당시 7일 이상 항정신병약물을 복용하지 않은 남자 정신분열증 환자 19명으로 하였고, PANSS에 의해 양성 아형 (12명) 및 음성 아형 (7명) 환자군으로 나누어 오전 9시에 PRL 기저치 측정과 함께 cimetidine(5mg/kg) 정액 점주 30분 후인 9시 30분에 cimetidine에 의한 PRL $T_{30}$치를 측정하여 다음과 같은 결과를 얻었다. 1) PRL 기저치는 세 군에서 차이가 없었다. 2) 기저와 $T_{30}$간에 PRL치의 변화는 세 군에서 증가했음을 보여주었다. 3) 기저와 $T_{30}$간에 PRL치 증가량에 대한 상대적인 비교에서 정상대조군과 양성 아형 환자군 간, 양성 아형 환자군과 음성 아형 환자군 간에는 차이가 없었으나 정상대조군과 음성 아형 환자군 간에서 상호 유의한 차이가 있었다(p<0.05). 상기 연구 결과들은 정상대조군에서 보다 음성 아형 환자군에서 cimetidine에 의한 PRL반응이 둔감하게 나타난 것을 보여준다 하겠다. 이러한 결과들은 정상대조군에서는 나타나지 않지만 남자 음성 아형 정신분열증 환자군에서 $5-HT_2$ 수용체 하향 조절을 포함하는 세로토닌계 활성 이상 소견이 나타날 수 있다는 가설(Meltzer등 1993) 들과 일치한다 하겠다.

• The Korean Journal of Pain
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• 제14권1호
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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.