• Title/Summary/Keyword: dopamine agonists

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일측성선조체의 6-OHDA손상 후 도파민효능약물 투여로 발현된 회전운동의 특성

  • 이순철;문민선
    • Journal of Ginseng Research
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    • v.21 no.1
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    • pp.61-67
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    • 1997
  • The present study examined the characteristics of behavior Induced by dopamine agonists following treatment with 6-hydroxydopamine(6-OHDA) unilaterally into left striatum in rats. 6-OHDA was administered at doses of 8,16 and 24 $\mu\textrm{g}$/$\mu\textrm{l}$(in 0.1% ascorbic acid) into dopaminergic neurons in left striatum of 7 weeks old rat under anesthetic. Locomotor activity was significantly decreased at 1 week following 6-OHDA-administration in 7 weeks old rats. The contralateral circling behavior was induced by apomorphine(5 mg/kg, i.v.) after 1 week following 6-OHDA(24$\mu\textrm{g}$/$\mu\textrm{l}$) treatment, and was further increased by repeated administration of apomorphine at 2, 3 and 4 weeks. The contralateral circling behavior was also induced by lisuride and 1-dopa in a dose dependent manner, but not by SK & F 82526 in 7 weeks old rats treated with 6-OHDA. The contralateral circling behavior was significantly higher in 21 weeks old rats but significantly lower In 35 weeks old rats when compared with 7 weeks old rats. The contralateral circling behavior induced by apomorphlne did not differ significantly in 7 and 35 weeks old male and female rats. These results suggest that 6-OHDA treatment into left striatum causes remarkable destrurtion of intrastriatal dopaminergic netcons leading to dopaminergic receptor supersensitivity. Thus, the contralateral circling behavior in duces by apomorphine may be used as indicator for neurodegenerative diseases.

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Dopamine Modulates Corticostriatal Synaptic Transmission through Both $D_1$ and $D_2$ Receptor Subtypes in Rat Brain

  • Lee, Hyun-Ho;Choi, Se-Joon;Kim, Ki-Jung;Cho, Hyeong-Seok;Kim, Seong-Yun;Sung, Ki-Wug
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.5
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    • pp.263-268
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    • 2005
  • Striatum has important roles in motor control, habitual learning and memory. It receives glutamatergic inputs from neocortex and thalamus, and dopaminergic inputs from substantia nigra. We examined effects of dopamine (DA) on the corticostriatal synaptic transmission using in vitro extracellular recording technique in rat brain corticostriatal slices. Synaptic responses were elicited by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. Corticostriatal population spike (PS) amplitudes were decreased ($39.4{\pm}7.9$%) by the application of $100{\mu}M$ DA. We applied receptor subtype specific agonists and antagonists and characterized the modulation of corticostriatal synaptic transmission by different DA receptor subtypes. $D_2$ receptor agonist (quinpirole), antagonist (sulpiride), and $D_1$ receptor antagonist (SKF 83566), but not $D_1$ receptor agonist (SKF 38393), induced significantly the reduction of striatal PS. Pretreatment neither with SKF 83566 nor sulpiride significantly affected corticostriatal synaptic inhibition by DA. However, the inhibition of DA was completely blocked by pretreatment with mixed solution of both SKF 83566 and sulpiride. These results suggest that DA inhibits corticostriatal synaptic transmission through both $D_1$ and $D_2$ receptors in concert with each other.

Regional difference in spontaneous firing inhibition by GABAA and GABAB receptors in nigral dopamine neurons

  • Kim, Yumi;Jang, Jinyoung;Kim, Hyun Jin;Park, Myoung Kyu
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.6
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    • pp.721-729
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    • 2018
  • GABAergic control over dopamine (DA) neurons in the substantia nigra is crucial for determining firing rates and patterns. Although GABA activates both $GABA_A$ and $GABA_B$ receptors distributed throughout the somatodendritic tree, it is currently unclear how regional GABA receptors in the soma and dendritic compartments regulate spontaneous firing. Therefore, the objective of this study was to determine actions of regional GABA receptors on spontaneous firing in acutely dissociated DA neurons from the rat using patch-clamp and local GABA-uncaging techniques. Agonists and antagonists experiments showed that activation of either $GABA_A$ receptors or $GABA_B$ receptors in DA neurons is enough to completely abolish spontaneous firing. Local GABA-uncaging along the somatodendritic tree revealed that activation of regional GABA receptors limited within the soma, proximal, or distal dendritic region, can completely suppress spontaneous firing. However, activation of either $GABA_A$ or $GABA_B$ receptor equally suppressed spontaneous firing in the soma, whereas $GABA_B$ receptor inhibited spontaneous firing more strongly than $GABA_A$ receptor in the proximal and distal dendrites. These regional differences of GABA signals between the soma and dendritic compartments could contribute to our understanding of many diverse and complex actions of GABA in midbrain DA neurons.

Overview of Periodic Limb Movements During Sleep (주기성 사지운동증의 개관)

  • Cyn, Jae-Gong
    • Sleep Medicine and Psychophysiology
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    • v.15 no.1
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    • pp.17-24
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    • 2008
  • Periodic leg movements during sleep (PLMS) are best described as repetitive stereotypical movements of the lower extremities characterized by dorsiflexion of the ankle, dorsiflexion of the toes and a partial flexion of the knee and sometimes the hip. The prevalence of PLMS is about 5-11% in adults and is predicted much higher than previously surveyed. They are also frequently found in various sleep disorders, several disorders not primarily affecting sleep, and patients taking psychiatric medications. Although they are rarely found in children, they are common findings in children referred to a pediatric sleep laboratory. The pathophysiology is strongly associated with decline of central dopaminergic function and closely related to arousal system during sleep. Benzodiazepines, levodopa, dopamine agonists and opioids are generally recommended for treatment but more controlled studies on the effectiveness are needed.

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Pharmacodynamic Drug-Drug Interactions Considered to be Added in the List of Contraindications with Pharmacological Classification in Korea (약물군-약물군 조합으로 도출한 약력학적 기전의 추가 병용금기성분)

  • Je, Nam Kyung;Kim, Dong-Sook;Kim, Grace Juyun;Lee, Sukhyang
    • Korean Journal of Clinical Pharmacy
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    • v.25 no.2
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    • pp.120-129
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    • 2015
  • Objectives: Drug utilization review program in Korea has provided 'drug combinations to avoid (DCA)' alerts to physicians and pharmacists to prevent potential adverse drug events or inappropriate drug use. Seven hundred and six DCA pairs have been announced officially by the Ministry of Food and Drug Safety (MFDS) by March, 2015. Some DCA pairs could be grouped based on the drug interaction mechanism and its consequences. This study aimed to investigate the drug-drug interaction (DDI) pairs, which may be potential DCAs, generated by the drug class-drug class interaction method. Methods: Eleven additive/synergistic and one antagonistic drug class-drug class interaction groups were identified. By combining drugs of two interacting drug class groups, numerous DDI pairs were made. The status and severity of DDI pairs were examined using Lexicomp and Micromedex. Also, the DCA listing rate was calculated. Results: Among 258 DDI pairs generated by the drug class-drug class interaction method, only 142 pairs were identified as official DCA pairs by the MFDS. One hundred and four pairs were identified as potential DCA pairs to be listed. QT prolonging agents-QT prolonging agents, triptans-ergot alkaloids, tricyclic antidepressants-monoamine oxidase inhibitors, and dopamine agonists-dopamine antagonists were identified as drug class-drug class interaction groups which have less than 50 % DCA listing rate. Conclusion: To improve the clinicians' adaptability to DCA alerts, the list of DCA pairs needs to be continuously updated.

Changes in Behavior and the Effect of Chronic-methamphetamine Following Lesions of the Nucleus Accumbens Septi in Rats (측좌핵(側坐核)(Nucleus Accumbens Septi) 파괴가 Methamphetamine의 작용에 미치는 영향)

  • Lee Soon-Chul
    • The Korean Journal of Pharmacology
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    • v.20 no.1 s.34
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    • pp.33-39
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    • 1984
  • The present study was undertaken to elucidate the chracteristics in behavioral changes of chronic doses of methamphetamine on open-field activity in rats. On the other hand, the nucleus accumbens septi(NAB), one of the major areas containing mesolimbic dopaminergic terminals, has been considered to be an important site of action for dopaminergic agonists. Therefore, it also designed to investigated influence of NAB lesions. on behavioral effects of chronic-methamphetamine. Caudal and rostral areas of NAB(cr-NAB) were lesioned by applying DC of 3.0 mA for 15 sec., simultaneously. The results were as follows: 1) The rats exhibited hyperactivity after chronic administration of methamphetamine 2) The cr-NAB-lesioned rats showed a significant increase in locomotor activity only at 2 days after NAB lesions 3) Methamphetamine-induced hyperactivity was significantly decreased in the NAB-lesioned rats, and stereotyped behavior was induced instead by the drug. 4) Dopamine content of striatum was significantly decreased and serotonin content of olfactory bulb was significantly increased in NAB-lesioned rats. These results suggest that NAB plays an important role in locomotor activity and methamphetamine-induced hyperactivity.

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A clinical report on the mild case of Parkinson's disease improved with Soyangin-Gihwangbeakho-tang (소양인(少陽人) 지황백호탕(地黃白虎湯)으로 호전된 경증(輕症) 파킨슨 환자에 대한 임상보고(臨床報告))

  • Go, Gyeong-Deok;Jeong, Sung-Hyun;Shin, Gil-Cho;Lee, Won-Chul;Lee, Ji-Hun
    • Journal of Sasang Constitutional Medicine
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    • v.14 no.3
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    • pp.153-159
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    • 2002
  • Parkinson's disease(PD) is characterized by chronic progress of mesencephalic dopaminergic neuronal death. Diagnostic criteria for PD require at least two of three motor sign: tremor, rigidity, or bradykinesia. Levodopa and the dopamine agonists are considerd first-line drug therapy. In the book ‘dongyi soose bowon(東醫壽世保元)’, Soyangin Gihwangbeakho-tang(地黃白虎湯) is used at Soyangin Interior-overheated-disease. This case is patient who is 69 years old lady, suffered by the tremor of jaw and a slight rigidity, bradykinesia etc. This patient was classified as Soyangin by features, somatotype and emotional patterns. She improved in the tremor of jaw and others with Gihwangbeakho-tang for 67days. The result revealed that Soyangin-Gihwangbeakho-tang was effected on the tremor of jaw and others with Parkinson's disease patient.

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A Cannabinoid Receptor Agonist N-Arachidonoyl Dopamine Inhibits Adipocyte Differentiation in Human Mesenchymal Stem Cells

  • Ahn, Seyeon;Yi, Sodam;Seo, Won Jong;Lee, Myeong Jung;Song, Young Keun;Baek, Seung Yong;Yu, Jinha;Hong, Soo Hyun;Lee, Jinyoung;Shin, Dong Wook;Jeong, Lak Shin;Noh, Minsoo
    • 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.

Strategy for Management of Giant Invasive Pituitary Adenoma

  • Yang, Hee-Seok;Kim, Oh-Lyong;Kim, Min-Soo;Kim, Sang-Woo;Chang, Chul-Hun;Cho, Soo-Ho
    • Journal of Korean Neurosurgical Society
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    • v.37 no.1
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    • pp.25-28
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    • 2005
  • Objective: Giant invasive pituitary adenoma looks histologically benign, but these tumors have an aggressive clinical course. The authors review 10 cases and discuss the results obtained and the strategy to use for the management of giant invasive pituitary adenoma. Methods: Out of a series of 155 pituitary adenomas treated surgically between 1994 and 2002, ten patients with giant invasive pituitary adenoma were selected and their clinical problems, radiologic findings, extent and invasiveness, hormonal and histologic findings and surgical results were analyzed retrospectively. Results: There were 4 male and 6 female patients, with an average age of 47 years and an average follow-up period of 42 months. The average size of tumor was 50.7mm. These tumors revealed severe invasions into surrounding structures. 8 patients underwent transsphenoidal approach(TSA) operations, 1 patient with transcranial operation and 1 patient with combined TSA and transcranial operation. In all cases, subtotal resection was performed. The histologic findings were 2 prolactinomas and 3 hormonal non-function adenomas. The therapies administered after surgical removal consisted of conventional fractionated radiotherapy (2 patients), treatment with dopamine agonists to control hyperprolactinemia (2 patients), and treatment with hormone replacement (2 patients). Conclusion: Giant invasive pituitary adenomas are characterized by different forms of expansion and invasiveness and variable clinical problems. Because of their aggressive expansion and invasiveness, there are many different strategies which can be considered for their management. The authors obtain good results by choosing conservative surgical removal and multidisciplinary treatments with serial radiological and hormonal follow-up.

Effects of dopaminergic receptor stimulation on Mg2+ regulation in the rat heart and isolated ventricular myocytes (흰쥐의 심장과 심근세포에서 dopaminergic 수용체 자극이 Mg2+ 조절에 미치는 영향)

  • Kang, Hyung-sub;Kim, Jong-shick;Kim, Jin-shang
    • Korean Journal of Veterinary Research
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    • v.39 no.3
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    • pp.463-471
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    • 1999
  • Magnesium($Mg^{2+}$) is one of the most abundant intracellular divalent cation. Although recent studies demonstrate that adrenergic receptor stimulation evokes marked changes in $Mg^{2+}$ homeostasis, the regulation of $Mg^{2+}$ by dopaminergic receptor stimulation is not yet known. In this work, we used dopaminergic agents to identify which type(s) of receptors were involved in the mobilization of $Mg^{2+}$ by dopaminergic receptor stimulation in the perfused rat hearts, isolated myocytes and circulating blood. The $Mg^{2+}$ content was measured by atomic absorbance spectrophotometry. Dopamine(DA), apomorphine(APO) and pergolide stimulated $Mg^{2+}$ efflux in the perfused rat hearts and these effects were inhibited by haloperidol or fluphenazine, nonselective dopaminergic antagonists. SKF38393, a selective doparminergic agonist, increased $Mg^{2+}$ efflux from the perfused hearts in dose dependant manners and SKF38393-induced $Mg^{2+}$ efflux was blocked by haloperidol. However, dopaminergic agonists-induced $Mg^{2+}$ efflux was potentiated in the presence of sulpiride or eticlopride, $D_2$-selective antagonist, from the perfused hearts. This increase of $Mg^{2+}$ efflux was blocked by haloperidol or imipramine. DA or pergolide increased in circulating $Mg^{2+}$ from blood. By contrast, PPHT stimulated $Mg^{2+}$ influx(a decrease in efflux) from the perfused hearts and circulating blood. PPHT-induced $Mg^{2+}$ influx was blocked by fluphenazine in the perfused hearts. DA-stimulated $Mg^{2+}$ efflux was inhibited by dopaminergic antagoinst in the isolated myocytes. In conclusion, the flux of $Mg^{2+}$ is modulated by DA receptor activation in the rat hearts. The efflux of $Mg^{2+}$ can be increased by $D_1$-receptor stimulation and decreased by $D_2$-receptor stimulation, respectively.

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