• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.208-219
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• 2001

The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

• Korean Journal of Biological Psychiatry
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• v.13 no.4
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• pp.299-304
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• 2006

Objectives : The purpose of the present study was to investigate whether the TaqI A polymorphism of dopamine receptor D2 gene(DRD2) is associated with Tourette syndrome(TS) and chronic motor tic disorder(CMT) in Korean population. Methods : DRD2 TaqI A RFLP genotyping was carried out with DNA extracted from blood samples of 75 patients with tic disorders(47 with TS and 28 with CMT) and 90 healthy subjects. Genotype and allelic frequencies for the DRD2 gene polymorphisms of the tic disorder group as a whole were compared to those of the control group. Separating the TS group, thereafter, the frequency of genotypes and alleles were compared to those of the controls. Results : The results demonstrated that genotype and allele distributions for the DRD2 gene polymorphism in the tic disorder as a whole, TS, and control groups were not significantly different. Conclusion : No association was found for DRD2 gene, TS and CMT. The data suggest that DRD2 gene may not be a useful marker for the prediction of the susceptibility of tic disorder.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.218-224
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• 2015

Endocannabinoids can affect multiple cellular targets, such as cannabinoid (CB) receptors, transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and peroxisome proliferator-activated receptor ${\gamma}$($PPAR{\gamma}$). The stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene transcription of the $CB_1$ receptor, TRPV1 and $PPAR{\gamma}$. In this study, the effects of three endocannabinoids, N-arachidonoyl ethanolamine (AEA), N-arachidonoyl dopamine (NADA) and 2-arachidonoyl glycerol (2-AG), on adipogenesis in hBM-MSCs were evaluated. The adipocyte differentiation was promoted by AEA whereas inhibited by NADA. No change was observed by the treatment of non-cytotoxic concentrations of 2-AG. The difference between AEA and NADA in the regulation of adipogenesis is associated with their effects on $PPAR{\gamma}$ transactivation. AEA can directly activate $PPAR{\gamma}$. The effect of AEA on $PPAR{\gamma}$ in hBM-MSCs may prevail over that on the $CB_1$ receptor mediated signal transduction, giving rise to the AEA-induced promotion of adipogenesis. In contrast, NADA had no effect on the $PPAR{\gamma}$ activity in the $PPAR{\gamma}$ transactivation assay. The inhibitory effect of NADA on adipogenesis in hBM-MSCs was reversed not by capsazepine, a TRPV1 antagonist, but by rimonabant, a $CB_1$ antagonist/inverse agonist. Rimonabant by itself promoted adipogenesis in hBM-MSCs, which may be interpreted as the result of the inverse agonism of the $CB_1$ receptor. This result suggests that the constantly active $CB_1$ receptor may contribute to suppress the adipocyte differentiation of hBM-MSCs. Therefore, the selective $CB_1$ agonists that are unable to affect cellular $PPAR{\gamma}$ activity inhibit adipogenesis in hBM-MSCs.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.135-145
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• 1988

Dopamine when given icv induces antidiuresis along with transient natriuretic tendency, and it has been suggested that both subtypes of central dopamine receptors may influence renal function differentially. This study was undertaken to delineate the role of central $D_2$ receptors employing domperidone (DOM), a selective $D_2$ antagonist. DOM icv elicited antidiuresis and antinatriuresis in doses ranging from 15 to $135{\mu}g/kg$. GFR and RPF as well as sodium excretion decreased. Systemic blood pressure increased slightly. Intravenous DOM did not elicit significant changes in sodium excretion. Denervation of the kidney abolished the hemodynamic change induced by icv DOM, but sodium excretion decreased on both innervated and denervated kidneys. No diuretic tendency was uncovered by the denervation. Dopamine, $150{\mu}g/kg$ icv, produced antidiuresis along with decreases in hemodynamics. These effects were not affected by DOM-pretreatment, and no natriuretic tendency was unveiled. Bromocriptine, a $D_2$ receptor agonist, $200{\mu}g/kg$ icv, elicited marked diuresis and natriuresis, which were completely abolished by DOM-pretreatment. Apomorphine, another prototype of $D_2$ agonist, $150{\mu}g/kg$ icv, produced diuresis and natrituresis with increases in renal hemdoynamics, followed by decreases in all parameters. DOM-pretreatment did not affect the renal hemodynamic effects, wherease the increases in urine flow and sodium excretion were markedly reduced by DOM, Present study suggests that central $200{\mu}g/kg$ receptors mediate natriuretic and diuretic influence to the kidney, possibly through mediation of natriuretic humoral factor, and provide further evidence supporting the hypothesis that central $200{\mu}g/kg$ receptors mediate antidiuretic influence via nerve pathway, whereas natriuresis are brought about through mediation of central $200{\mu}g/kg$ receptors.

• Korean Journal of Biological Psychiatry
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• v.2 no.2
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• pp.218-236
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• 1995

The author studied prognostic indicators of sixty Korean male alcoholics in psychological, social and biological aspects who were divided into abstinent and drinking groups. Thirty patients were assigned to each group. They were controlled in age and sex. Both groups were compared in terms of the demographic characteristics, past drinking history, treatment history, famaily history, ego strength and personality factors differences and distribution of dopamine $D_2$ receptor gene Al allele. Also the author studied relation of clinical course, alcoholic family history and dopamine $D_2$ receptor gene Al allele in both groups. The results were as follows; 1) The abstinent group had higher rate of married state, higher economic status, longer education years and maintained more stable job than the drinking group. But made no differences in occupation and religion. 2) The abstinent group showed higher rate of living with family members than the drinking group, and wives and fellows of the alcoholics anonymous were important factors for maintenance of abstinence. Family loading and parent's characters were not different. 3) The abstinent group had longer maximal length of abstinence but mean amount of alcohol consumption per day were larger than the drinking group. But there were no differences in duration of past drinking, drinking pattern, main drinking time, first drinking age and preference of the kind of alcoholic beverage in the past drinking history. 4) The abstinent group showed stronger treatment motivation, absolute abstinence in treatment goal, more voluntary adimission and maintained longer therapeutic relationship otter discharge than the drinking group. But both groups showed negative attitude toward antabuse therapy. 5) The abstinent group had higher mean score in ego strength scale than the drinking group. 6) In the personality factor questionnaire, the abstinent group showed strong laugh poise and the trait of praxernia, conservatism personality but the drinking group showed tough poise, the trait of weak ego strength(unstableness) and tough mindedness personality. 7) In comparision of dopamine $D_2$ receptor gene A1 allele, the prevalence of A1 allele was seventy percent and the frequency was 0.38 in the abstinent group. The prevalence of A1 allele was sixty percent and the frequency was 0.42 in the drinking group. Both groups were not significantly different in A1 allele prevalence and frequency. 8) In comparision of dopamine $D_2$ receptor gene A1 allele according to alcoholic family history, the prevalence of A1 allele was seventy percent and the frequency was 0.43 in the family history positive group. The prevalence of A1 allele was sixty-one percent and the frequency was 0.38 in the family history negative group. Both groups were not significantly different in A1 allele prevalence and frequency. In comparision of past drinking history according to alcoholic family history, the family history positive group showed earlier first drinking and problem drinking, but the family history negative group hod longer duration of past drinking. The mean amount of alcohol consumption per day, the longest duration of abstinence and Alcoholism Screening Test of Seoul Natoinal Mental Hospital(NAST) results were not significant. In conclusion, the results suggest that successful prognostic indicators of Korean alcoholics are married state, higher economic status, longer education years, stable job, living with family members, longer abstinence during past drinking history, strong treatment motivation, absolute abstinence in treatment goal, voluntary adimission, maintained therapeufic relationship, strong ego strength and the trait of praxernia, conservatism personality. But occupation, religion, alcoholic family history, parent's characters, duration of past drinking, drinking pattern, main drinking time, first drinking age, preference of the kind of alcoholic beverage, attitude to antabuse therapy and distribution of dopamine $D_2$ receptor A1 allele were not significantly related to the prognostic indicators of Korean alcoholics.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.360-366
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• 2000

The in vivo binding of dopamine (DA) radioligands to $D_2$receptors can be affected by competition with endogenous dopamine. In the present study, we used a brain slice preparation that provides more controlled conditions than in vivo preparations in order to examine the relationship between synaptic DA and the binding of [$^3H$] raclopride to $D_2$receptors. We also estimated the synaptic DA concentration in rat striatal slices by determining the changes in [$^3H$] raclopride binding. To correlate the changes in [$^3$H]raclopride binding with the concentration of synaptic DA, the kinetic parameters were determined. [$^3H$] Raclopride reached equilibrium binding conditions within two hours. The K value for DA in inhibiting [$^3$H]raclopride binding was about 2.2 nM. The increase in synaptic DA evoked by electrical stimulation decreased the striatal binding of [$^3H$] raclopride in a frequency-dependent manner. Increases in the DA concentration evoked by amphetamine (AMPH) or cocaine decreased [$^3H$] raclopride binding by 74% or 20%, respectively, corresponding to increases in the synaptic DA concentrations of 1.6 nM or 0.6 nM, respectively. Pargyline also decreased [$^3H$] raclopride binding by 36%corresponding at a concentration of 1.2 nM. In contrast, the depletion of synaptic DA by $\alpha$-methyl-p-tyrosine ($\alpha$-MpT) increased the specific binding of [$^3H$] raclopride by 43%when the DA concentration was decreased to 0.7 nM. The changes in the DA concentration at the synapse were responsible for the changes in the striatal binding of [$^3H$] raclopride. The values calculated in this study may therefore approximate the changes in the synaptic DA concentration in rat striatal slices following manipulation.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.219-224
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• 2012

Understanding how the b-wave of the electroretinogram (ERG) is generated by full-field light stimulation is still a challenge in visual neuroscience. To understand more about the origin of the b-wave, we studied the contributions of gap junctions to the ERG b-wave. Many types of retinal neurons are connected to similar and different neighboring neurons through gap junctions. The photopic (cone-dominated) ERG, stimulated by a small light beam, was recorded from goldfish (Carassius auratus) using a corneal electrode. Data were obtained before and after intravitreal injection of agents into the eye under a photopic illumination level. Several agents were used to affect gap junctions, such as dopamine D1 and D2 receptor agonists and antagonists, a nitric oxide (NO) donor, a nitric oxide synthase (NOS) inhibitor, the gap junction blocker meclofenamic acid (MFA), and mixtures of these agents. The ERG b-waves, which were enhanced by MFA, sodium nitroprusside (SNP), SKF 38393, and sulpiride, remained following application of a further injection of a mixture with MFA. The ERG b-waves decreased following $N^G$-nitro-L-arginine methyl ester (L-NAME), SCH 23390, and quinpirole administration but were enhanced by further injection of a mixture with MFA. These results indicate that gap junction activity influences b-waves of the ERG related to NO and dopamine actions.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.94-98
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• 2004

Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells) and the nitric oxide production from macrophage cells (RAW 264.7) were studied. Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT, haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion ($IC_{50} value, 5 \mu$ M). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor ($Fc\varepsilonRI$), such as Syk, $PLC\gamma1$, and $PLC\gamma2$.; This suggested that these signaling components were not involved in the inhibition of the mast cell degranulation by these compounds. On the other hand, dopamine, bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide production from RAW 264.7 cells ($IC_{50}$ values, 10-20$\mu$M). Bromocriptine, a dopamine agonist that is routinely used for the treatment of Parkinsons disease, inhibited the expression of the inducible nitric oxide synthase at an early stage of the LPS-induced protein expression in a dose-dependent manner. The results suggested that these dopaminergic agents, when used for the treatment of dopamine receptors-related diseases, such as Schizophrenia or Parkinsons disease, might have additional beneficial effects.

• BMB Reports
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• v.31 no.3
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• pp.264-268
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• 1998

Dopamine (DA) acts on swimming motor neurons (SMNs) of Polyorchis penicillatus as an inhibitory neurotransmitter by hyperpolarizing their membrane potentials, which results from the activation of voltagesensitive potassium channels mediated through a $D_2-type$ receptor. In addition, DA, and not the hyperpolarized membrane potential, directly decreased the input resistance of SMNs by ca. 50% from 1.42 to 0.68 $G{\Omega}$. It strongly indicates that DA can shunt other excitatory synaptic signals onto SMNs where DA usually elicited much greater responses in their neurites than soma. All these evidences suggest that DA may operate in this primitive nervous system in dual modes as an inhibitory neurotransmitter and neuromodulator as well.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.101-101
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• 1995

The effects of ginseng prepation, Adaptagen$\^$R/ (AD), on the central dopaminergic nervous system in the learning-impaired rats were studied. The learning impaired rats were rendered by the intracerebroventricular infusion of ethylcholine aziridium (AF64A), 3 nmol/each side. Three days after the infusion of AF64A, AD were orally intubated daily for five days, 200 mg/kg. The control groups were intubated with distilled water. Twenty four hours after the last intubation, The changes in the specific bindings of dopamine receptors, the concentrations of dopamine (DA) and metabolites, The activities of tyrosine hydrosylase (TH) and monoamine oxidase (MAO) were analyzed using receptor radiography, HPLC-ECD and the methods in enzyme-assays, respectively.