• Biomolecules & Therapeutics
• /
• v.17 no.1
• /
• pp.32-42
• /
• 2009

The purpose of the present study was to examine the effect of dihydrexidine, a full $D_1$ receptor agonist, on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland, and to establish its mechanism of action. Dihydrexidine (10-100 ${\mu}M$), perfused into an adrenal vein for 60 min, relatively produced dose- and time-dependent inhibition in the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Dihydrexidine itself did fail to affect basal CA output. Also, in adrenal glands loaded with dihydrexidine (30 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$), an activator of L-type $Ca^{2+}$ channels, cyclopiazonic acid (10 ${\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, and veratridine, an activator of voltage-dependent $Na+$ channels (10 ${\mu}M$), were also markedly inhibited, respectively. However, in the simultaneous presence of dihydrexidine (30 ${\mu}M$) and R (+)-SCH23390 (a selective antagonist of $D_1$ receptor, 3 ${\mu}M$), the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory responses by dihydrexidinetreatment alone. In conclusion, these experimental results suggest that dihydrexidine significantly inhibits the CA secretion evoked by cholinergic stimulation (both nicotinic and muscarinic receptors) and membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of dihydrexidine may be mediated by inhibiting influx of both $Ca^{2+}$ and $Na^+$ into the cytoplasm as well as by suppression of $Ca^{2+}$ release from cytoplasmic calcium store through activation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells.

• Journal of TMJ Balancing Medicine
• /
• v.10 no.1
• /
• pp.12-20
• /
• 2020

Objectives: Tourette syndrome (TS) is a disease that occurs evenly in many social classes. Despite the long experience of drug treatment, the preference is low due to various side effects. The aim of this study was to discover herbal medicine resources through network pharmacology analysis predicted to be useful for Tourette syndrome. Methods: We used Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) to identify herbal medicines that can be used for TS by using network pharmacology research methods and to predict the mechanism of action. After evaluating compounds of each identified herb, molecular target proteins and mechanisms of action were analyzed, focusing on compounds that are likely to exhibit clinical activity in consideration of the pharmacokinetic parameters of these individual compounds. Results: Fifty nine ingredients such as atropine, veraguensin, and nuciferin among the compounds contained in 48 types of medicinal herbs such as Daturae Flos (洋金花), Salviae Radix (丹参), and Nelumbinis Plumula (蓮子心) act on the D(2) dopamine receptor, which is a protein involved in the development of TS. It has been found that atropine, veraguensin, and nuciferin are highly likely to exhibit activity by acting on the G protein-coupled receptor signaling pathway. Conclusions: It can be used in conjunction with non-invasive treatment means such as FCST Yinyang Balancing Appliance with herbal therapy to bring about a significant therapeutic effect, and it will be possible to develop a treatment that can replace drug therapy used in Western medicine.

• CELLMED
• /
• v.13 no.14
• /
• pp.15.1-15.15
• /
• 2023

Background and objective: A new formular CPC22 consists of Cynanchum wilfordii root, Pueraria thomsonii flower, and Citrus unshiu peel and has been developed to improve the postmenopausal symptoms. The research intended to evaluate whether CPC22 would regulate bone loss, hot flashes, and dysregulated lipid metabolism in ovariectomized (OVX) postmenopausal mice. Method: The OVX mice were orally administered with CPC22 daily for 7 weeks. Results: CPC22 regulated OVX-induced bon loss by enhancing serum osteoprotegerin, alkaline phosphatase, and osteocalcin levels and diminishing serum receptor-activator of the NF-κB ligand (RANKL), collagen type 1 cross-linked N-telopeptide, and tartrate-resistant acid phosphatase levels. As a result of CPC22 treatment, notable decreases in tail skin temperature and rectal temperature were observed, along with diminishment in hypothalamic RANKL and monoamine oxidase A levels and enhancement in hypothalamic serotonin (5-HT), norepinephrine, dopamine, 5-HT2A, and estrogen receptor-β levels. CPC22 enhanced levels of serum estrogen and diminished levels of serum follicle-stimulating hormone and luteinizing hormone. CPC22 regulated levels of serum lipid metabolites, including total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Furthermore, CPC22 diminished levels of serum blood urea nitrogen, creatine kinase, alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase and restored vaginal dryness without affecting uterus atrophy index and vagina weights. Conclusion: Therefore, these results indicated that CPC22 improves OVX-induced bone loss, hot flashes, and dysregulated lipid metabolism by compensating for estrogen deficiency without side effects, suggesting that CPC22 may be used for the prevention and treatment of post menopause.

• The Korean Journal of Pharmacology
• /
• v.30 no.3
• /
• pp.291-297
• /
• 1994

Our purpose was to gain insight into a possible modulatory role for ${\mu},\;{\delta},\;and\;{\kappa}$ opioid receptors by neuroleptics (chlorpromazine, thioridazine, haloperidol, sulpiride, and pimozide) in chronic morphine 5 mg/kg and 20 mg/kg treated mouse striatum. We attempted quantitative receptor assays using highly specific radioligands, $[^3H]\;DAGO\;([D-Ala^2,\;N-Mephe^4,\;Glycol^5]\;enkephalin)$, $[^3H]DPDPE\;([D-Pen^2,\;D-Pen^5]\;enkephalin)$ and $[^3H]\;DPN(diprenorphine)$ to measure the binding affinity in the experimental groups. The decrease of $[^3H]DAGO$ binding was potentiated by sulpiride and pimozide in the chronic morphine treatment (5 mg/kg and 20 mg/kg). The decrease of $[^3H]DPDPE$ binding was inhibited by chlorpromazine, thioridazine, haloperidol, sulpiride, and pimozide in chronic morphine treatment (5 mg/kg and 20 mg/kg). The decrease of $[^3H]\;DPN$ binding was significantly inhibited by chlorpromazine, thioridazine, sulpiride, and pimozide in chronic morphine 20 mg/kg treatment. $[^3H]\;DPN$ binding on the neuroleptics was antagonized by naloxone pretreatment in chronic morphine 20 mg/kg treatment. These findings suggest that neuroleptics influence opposing tonically active on the ${\delta},\;and\;{\kappa}$ opioid receptor compared with ${\mu}$ opioid receptor in the chronic morphine treated mouse striatum.

• The Korean Journal of Nuclear Medicine
• /
• v.39 no.6
• /
• pp.421-429
• /
• 2005

Purpose: It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with $[^{11}C]raclopride$. Materials and Methods: Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of $24.4{\pm}1.7$ years) were enrolled in this study $[^{11}C]raclopride$, a dopamine D2 receptor radioligand, was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes ($3{\times}20s,\;2{\times}60s,\;2{\times}120s,\;1{\times}180s\;and\;22{\times}300s$). following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar)/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. Results: The mean decrease in binding potential of $[^{11}C]raclopride$ between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7%, 4.0% and 7.8%, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, p=0.04). Conclusion: These data demonstrate that in vivo imaging with $[^{11}C]raclopride$ PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount or nicotine administered bt smoking.

• The Korean Journal of Nuclear Medicine
• /
• v.38 no.4
• /
• pp.294-299
• /
• 2004

Purpose: Both human NIS and mutant $D_2R$ transgenes are proposed as reporting system in transplanted cell tracking. Using hepatoma cell lines, we constructed a dual reporter system containing human sodium-iodide symporter (hNIS) and dopamine 2 receptor ($D_2R$) and compared its characteristics. Materials and Methods: The recombinant plasmid ($pIRES-hNIS/D_2R$) was constructed with IRES (internal ribosome entry site) under control of the CMV promoter $pIRES-hNIS/D_2R$ was transfected to human hepatoma SK-Hep1 cell line with lipofectamine. HEP-ND ($SK-Hep1-hNIS/D_2R$) cells stably expressing hNIS and $D_2R$ was established by selection with G418 for two weeks. RT-PCR was performed to investigate the expression of both hNIS and $D_2R$ genes. The expressions of hNIS and $D_2R$ were measured by $^{125}I$ uptake assays and receptor binding assays. Specific binding of $D_2R$ to $[^3H]spiperone$ was verified by Scatchard plot with (+) butaclamol as a specific inhibitor. $K_d\;and\;B_{max}$ values were estimated. The correlation between hNIS and $D_2R$ expression was compared by using each clone. Results: Similar quantities of hNIS and $D_2R$ genes were expressed on HEP-ND as RT-PCR assays. HEP-ND cells showed 30 to 40 fold higher radioiodine uptakes than those of parental SK-Hep1 cells. $^{125}I$ uptake in HEP-ND cells was completely inhibited by $KClO_4$, a NIS inhibitor Specific binding to HEP-ND cells was saturable and the $K_d\;and\;B_{max}$ values for HEP-ND cells were 2.92 nM, 745.25 fmol/mg protein and 2.91nM, 1323 fmole/mg protein in two clones, respectively. The radioiodine uptake by hNIS activity and $D_2R$ binding was highly correlated. Conclusion: We developed a dual positron and gamma imaging reporter system of hNIS and $D_2R$ in a stably transfected cell line. We expect that $D_2R$ and hNIS genes can complement mutually as a nuclear reporting system or that $D_2R$ can be used as reporter gene when hNIS gene were used as a treatment gene.

• Journal of Oriental Neuropsychiatry
• /
• v.24 no.3
• /
• pp.257-262
• /
• 2013

Objectives : Aripiprazole is unique drug among the SGA (Second generation antipsychotics) in its pharmacology and pharmacokinetics,but is similar in clinical efficacy. Aripiprazole acts as a partial agonist at dopamine D2 receptors, activating the receptor but eliciting a reduced response compared to the natural neurotransmitter. There are some side effects of aripiprazole, the most common side effects of aripiprazole are headache, nausea, vomiting, insomnia, tremor, constipation and EPS. Difficulty in opening eyes is not defined EPS yet, but it is a rare but important side-effect symptom of aripiprazole. Methods : This article is about a case of side-effect symptom of aripiprazole, 26-year-old single female suffering from schizophrenia had difficulty in opening eyes while she was taking antipsychotics. During the hospitalization, the relaxation therapy is helpful not only to reduce tension in the eyelids but also to headache. Results : It is important that early recognition of aripiprazole-induced oculogyric dystonia can prevent life-threatening complications. Education medical staff to this easily treatable reaction will improve overall quality of health care. Conclusions : This case notifies the need for awareness of the risk of acute oculogyric dystonia in adolescent female patients receiving aripiprazole.

• YAKHAK HOEJI
• /
• v.54 no.4
• /
• pp.300-308
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.19 no.1
• /
• pp.60-64
• /
• 2012

Objectives : This study was designed to investigate the association between the dopamine D2 receptor (DRD2) genetic polymorphism [TaqIB (rs17294542) and TaqID (rs1800498)] and patients with schizophrenia. Methods : TaqIB (rs17294542) and TaqID (rs1800498) polymorphism of the DRD2 gene were typed in 100 patients with schizophrenia and 109 normal controls. Results : There were no statistical differences in genotype and allele distribution of TaqIB (rs17294542) and TaqID (rs1800498) genetic polymorphism between patients with schizophrenia and normal controls. Conclusions : These results suggest that the TaqIB (rs17294542) and TaqID (rs1800498) polymorphisms of the DRD2 gene may not be associated with schizophrenia in the Korean population.

• Korean Journal of Biological Psychiatry
• /
• v.20 no.4
• /
• pp.129-135
• /
• 2013

Aggression can be defined as 'behavior intended to harm another' which can be seen both from humans and animals. However, trying to understand aggression in a simplistic view may make it difficult to develop an integrated approach. So, we tried to explain aggression in a multidisciplinary approach, affected by various factors such as neuroanatomical structures, neurotransmitter, genes, and sex hormone. Parallel with animal models, human aggression can be understood with two phenomena, offensive aggression and defensive aggression. Neurobiological model of aggression give a chance to explain aggression with an imbalance between prefrontal regulatory influences and hyper-reactivity of the subcortical areas involved in affective evaluation, finally in an aspect of brain organization. Serotonin and GABA usually inhibit aggression and norepinephrine while glutamate and dopamine precipitate aggressive behavior. As there is no one gene which has been identified as a cause of aggression, functions between gene to gene interaction and gene to environment interaction are being magnified. Contributions of sex hormone to aggression, especially molecular biologic interaction of testosterone and regulation of estrogen receptor have been emphasized during the research on aggression. This multidisciplinary approach on aggression with types, neurochemical bases, and animal models can bring integrated interpretation on aggression.