• 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.

• Journal of Pharmacopuncture
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• v.23 no.1
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• pp.1-7
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• 2020

Nicotine, primary component of tobaco produces craving and withdrawal effect both in humans and animals. Nicotine shows a close resemblance to other addictive drugs in molecular, neuroanatomical and pharmacological, particularly the drugs which enhances the cognitive functions. Nicotine mainly shows its action through specific nicotinic acetylcholine receptors located in brain. It stimulates presynaptic acetylcholine receptors thereby enhancing Ach release and metabolism. Dopaminergic system is also stimulated by it, thus increasing the concentration of dopamine in nuclear accumbens. This property of nicotine according to various researchers is responsible for reinforcing behavioral change and dependence of nicotine. Various researchers have also depicted that some non dopaminergic systems are also involved for rewarding effect of nicotinic withdrawal. Neurological systems such as GABAergic, serotonergic, noradrenergic, and brain stem cholinergic may also be involved to mediate the actions of nicotine. Further, the neurobiological pathway to nicotine dependence might perhaps be appropriate to the attachment of nicotine to nicotinic acetylcholine receptors, peruse by stimulation of dopaminergic system and activation of general pharmacological changes that might be responsible for nicotine addiction. It is also suggested that MAO A and B both are restrained by nicotine. This enzyme helps in degradation dopamine, which is mainly responsible for nicotinic actions and dependence. Various questions remain uninsurable to nicotine mechanism and require more research. Also, various genetic methods united with modern instrumental analysis might result for more authentic information for nicotine addiction.

• Korean Journal of Veterinary Research
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• v.32 no.2
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• pp.165-173
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• 1992

The present study was carried out to investigate the effects of dopaminergic drugs and the role of specific dopamine(DA) receptors on the release of TSH, $T_4$ and $T_3$. Serum TSH levels (cold-induced, $4{^{\circ}C}$) were determined using RIA(radioimmunoassay) at 30 min after administration of dopamine agonists and antagonists. Serum $T_4$ and $T_3$ levels were detected after these dopaminergic drugs were administered subcutaneously twice a day for a week. The results of the study are summarized as follows : Apomorphine, a nonspecific DA receptor agonist, produced a dose-depedent decrease in serum TSH, $T_4$ and $T_3$ levels. However, only low doses (0.3, 1.0mg/kg) of SKF38393, a specific $D_1$-receptor agonist, produced a decrease in serum lelvels of TSH. I,Y171555, a specific $D_2$-receptor agonist, produced a dose dependent decrease in serum TSH, $T_4$ and $T_3$ levels. However, SCH23390, a specific $D_1$-receptor antagonist, produced a decrease except in serum T levels which were increased dose dependently. High doses (1.0, 3.0mg/kg) of sulpiride, a specific $D_2$-receptor antagonist, made a increase in the serum levels of TSH and $T_3$. The effects of dopaminergic drugs in serum TSH and $T_4$ levels was potentiated by the pretreatment of apomorphine. The overall results of this study suggest that the regulation of TSH, $T_4$ and $T_3$ secretion were mediated via specific $D_1$ and $D_2$ receptor.

• Animal cells and systems
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• v.4 no.3
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• pp.287-292
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• 2000

The present work examined the role of gonadotropin-releasing hormone (GnRH) and dopaminergic drugs on the secretion of maturational gonadotropin (GTH II) in relation to testosterone m treatment. This study provides evidence that the plasma GTH II levels are increased by T treatment in precocious males, but not in the immature animal. In addition, GnRH analogue (GnRHa) alone significantly increased the plasma GTH II secretion in immature rainbow trout treated with T, as well as in T-treated and T-untreated precocious males. However, injection with either dopamine (DA) or domperidone (DOM; DA D2 receptor antagonist) alone did not alter the basal plasma GTH 11 secretion in all experimental groups. The secretion of GTH II in the T-treated precocious males was remarkably influenced by GnRHa or combination of dopaminergic drugs. Notably, the effects of dopaminergic drugs on GnRHa-induced GTH II secretion w8s prolonged by T in precocious males. In T-treated immature animals, GnRHa-induced GTH II secretion was Increased only by a dose DOM (10$\mu$g/g body n) but not by higher dose DOM (100$\mu$/g body wt). In the T-untreated immature rainbow trout, however, plasma GTH 11 secretion was not influenced by the same treatments. Therefore, these results indicate that DA may be acting indirectly by blocking the effect of GnRH on GTH II secretion in vivo. T may act to modulate the relative contribution by the stimulatory (GnRH) and inhibitory (DA) neuroendocrine factors, which would ultimately determine the pattern of GTH II secretion.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.49-52
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• 2008

Parkinson's disease is characterized by motor disturbances and dopaminergic neurodegeneration. parkin and PINK1, two most critical Parkinson's disease-associated genes, have been intensively studied to address the underlying molecular pathogenesis of the disease, but our understanding still remains unclear. Through generation and characterization of Drosophila mutants for PINK1, we show that PINK1 is required for mitochondrial integrity and function in both indirect flight muscles and dopaminergic neurons. Surprisingly, we find that PINK1 mutants share striking phenotypic similarities with parkin mutants. Indeed, transgenic expression of parkin dramatically ameliorates all PINK1 loss-of-function phenotypes, but not vice versa, implicating that Parkin acts downstream of PINK1 in maintaining mitochondrial integrity and function in both muscles and dopaminergic neurons. With the establishment of the PINK1-Parkin pathway, we are trying to further investigate the detailed molecular relationship between PINK1 and Parkin using both mammalian dopaminergic neuronal cells for biochemical analysis and Drosophila model animal for genetic analysis. We believe that elucidating the molecular function of Parkinson's disease-associated genes will be of big help for the ultimate understanding of the pathogenic mechanism of this disease and also for the development of effective drugs for Parkinson's disease.

• Sleep Medicine and Psychophysiology
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• v.18 no.1
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• pp.5-9
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• 2011

Sleep-related eating disorder (SRED) is a newly recognized parasomnia that describes a clinical condition of compulsive eating under an altered level of consciousness during sleep. Recently, it is increasingly recognized in clinical practice. The exact etiology of SRED is unclear, but it is assumed that SRED might share features of both sleepwalking and eating disorder. There have been also accumulating reports of SRED related to the administration of various psychotropic drugs, such as zolpidem, triazolam, olanzapine, and combinations of psychotropics. Especially, zolpidem in patients with underlying sleep disorders that cause frequent arousals, may cause or augment sleep related eating behavior. A thorough sleep history is essential to recognition and diagnosis of SRED. The timing, frequency, and description of food ingested during eating episodes should be elicited, and a history of concurrent psychiatric, medical, sleep disorders must also be sought and evaluated. Interestingly, dopaminergic agents as monotherapy were effective in some trials. Success with combinations of dopaminergic and opioid drugs, with the addition of sedatives, has also been reported in some case reports.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.272.2-272.2
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• 2003

Dopamine ${\beta}$-hydroxylase (DBH) synthesizes norepinephrine from dopamine under the presence of ascorbate as a coenzyme. Dopamine is transported into the vesicles of the varicosity, where the synthesis and the storage of norepinephrine take place. Some drugs such as DBH inhibitors, dopaminergic agonists,etc. are known to assist in treating Parkinson's disease. (omitted)

• Biomolecules & Therapeutics
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• v.11 no.4
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• pp.214-223
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• 2003

Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) have become popular recreational drugs of abuse in many countries. Although the neurotoxic damage caused by METH and MDMA is characterized by degeneration of the dopaminergic and serotonergic systems in brain, the molecular and cellular mechanisms remain to be clarified. Therefore, the purposes of this study were to confirm the capability of METH and MDMA to induce apoptosis and to clarify the action of its molecular mechanism by using serotonergic JAR cells and dopaminergic SK-N-SH cells. METH and MDMA were dose-dependently cytotoxic to human serotonergic JAR cells and dopaminergic SK-N-SH cells. The morphological change of apoptosis was found in Giemsa staining and TUNEL and further verified in DNA fragmentation analysis. Immunoblotting analysis revealed proteolytic cleavage of caspase-3 and -9 and change of bcl-2 and bax proteins. These results suggest that METH and MDMA may induce caspase-dependent apoptosis via the mitochondrial cell death pathway and METH and MDMA-induced neurotoxicity may happen to broadly and independently of both dopaminergic and serotonergic systems.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.168-173
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• 1998

A single administration of cocaine (CO), morphine (MOR) and methamphetamine (MA) showed hyperactivity in mice. Ginseng total saponin (GTS), ginsenosides Rbl and Rgl inhibited the hyperactivity induced by the drugs. The repeated administration of CO, MOR and MA showed the development of psychological dependence showing a.: the development of conditioned place preference (CPP) in mice and the development of dopamine (DA) receptor supersensitivity showing as sensitization of the drugs. GTS and Rgl inhibited the development of not only psychological dependence but also of DA receptor supersensitivity induced by CO and MA Rbl prevented also the development of psychological dependence and DA receptor supersensitivity induced by CO and MA but not by MOR. These results suggest that the development psychological dependence induced by the drugs is closely related with the development of DA receptor supersensitivity since both phenomena were inhibited by them. Apomorphine induced climbing behavior was also inhibited by G75 but not by both of Rbl and Rgl, indicating that GTS modulate dopaminergic action at both of pre and postsynaptic sites, but both of Rbl and Rgl , only at the presynaptic site. These results suggest that active components acting at the postsynaptic site exist in GTS. In this study, it was found that GTS, ginsenosides Rbl and Rgl inhibited tyrosine hydroxylase (TH) and these components exerted inhibitory effects on both Cal' currents and $\Delta$ Cm in rat adrenal chromaffin cells. These results suggest that G75 and ginsenosides regulate catecholamine synthesis and secretion. Meanwhile, it has been demonstrated that Rbl, at high doses has more powerful inhibition of cartecholamine secretion at the presynaptic site than Rbl. Therefore, it was presumed that inhibition of morphine induced psychological dependence by Rgl, but not by Rbl results from differences in the extent of this inhibitory action on dopaminergic synthesis and secretion.

• Journal of Ginseng Research
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• v.19 no.3
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• pp.197-201
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• 1995

The present study was undertaken to elucidate the behavioral characteristics of nootropic candidates, entrophenoxine, N-methyl-D-glucamine, piracetam and red ginseng saponin components on stereotyped sniffing behavior induced by apomorphine in rats. Apomorphine, a direct dopaminergic receptor agonist, induced stereotyped behaviors including sniffing licking growing and biting in a dosedependent manner, and that behaviors were completely inhibited when measured at 1 week after 6-ydroxydopamine(6-HDA) treatment. Centrophenoxine, N-methyl-D-glucamine, red ginseng total saponin(TS), panaxatriol (PT), and Rg1 enhanced but panaxadiol (PD) inhibited, whereas piracetam and Rb1 were not effective of the sterotyped sniffing behavior induced by apomorphine(1mg/kg). The enhanced stereotyped behavior by centrophenoxine, N-methyl-D-glucamine, red ginseng total saponin, panaxatriol(PT), and Rg1 seems to have a similarity to entrophenoxine, N-methyl-D-glucamate in modulating of dopaminergic neuroal activity and also my be useful for the nootropic candidates.