Effects of Interaction Between Dopamine D2 Receptor and Monoamine Oxidase A Genes on Smoking Status in Young Men

2015 ◽  
Vol 17 (4) ◽  
pp. 422-428 ◽  
Author(s):  
Chih-Ling Huang ◽  
Wei-Chih Ou ◽  
Pei-Lain Chen ◽  
Chen-Nu Liu ◽  
Mei-Chih Chen ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Dopamine D2 Receptor ◽  
Smoking Status ◽  
D2 Receptor ◽  
Dopamine Metabolism ◽  
Monoamine Oxidase A ◽  
Self Report ◽  
Urinary Cotinine ◽  
Dopamine D2 ◽  
Taiwanese Men

Although the effect of gene–gene interaction on nicotine–dopamine metabolism for smoking behavior has been reported, polymorphisms of dopamine D2 receptor ( DRD2) and monoamine oxidase A ( MAOA) have not been simultaneously examined among smokers. In this study, 481 young Taiwanese men completed a self-report questionnaire on smoking status, and data were obtained on polymorphisms of DRD2 rs1800497, DRD2 rs1079597, MAOA rs309850, and MAOA rs1137070, urinary nicotine, and urinary cotinine. In a comparison of 261 current smokers and 220 never smokers, odds ratios ( ORs) for the development of smoking in all genotypes were not statistically significant. Among smokers with DRD2 rs1079597 GG// MAOA rs309850 3-repeat, the OR of heavier smoking was 2.67 times higher (95% confidence interval [CI]: [1.08, 6.59], p = .031) and the score on the Fagerstrom test for nicotine dependence was higher (4.26 vs. 2.83) than in those with DRD2 rs1079597 AA// MAOA rs309850 3-repeat. Adjusted urinary cotinine concentration was significantly different between those two groups (median value: 95.83 ng/μl vs. 133.24 ng/μl, respectively, p = .045). These findings suggest that the interaction of DRD2 rs1079597 and MAOA rs309850 3-repeat affects smoking intensity in young Taiwanese men.

scholarly journals Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4614
Author(s):  
Christopher Cerda-Cavieres ◽  
Gabriel Quiroz ◽  
Patricio Iturriaga-Vásquez ◽  
Julio Rodríguez-Lavado ◽  
Jazmín Alarcón-Espósito ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Dopamine D2 Receptor ◽  
General Structure ◽  
D2 Receptor ◽  
Docking Studies ◽  
Monoamine Oxidase A ◽  
Binding Modes ◽  
Dopamine D2 ◽  
Mao A ◽  
Nanomolar Range

A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a–o) and (2-{4-[3-(1H-3-indolyl)-propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a–l) were synthesized and evaluated as novel multitarget ligands towards dopamine D2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D2 receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D2 receptor (D2/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure–activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q2 = 0.625, 0.523 for CoMFA and CoMSIA and r2ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).

Dopamine D2 agonists in the treatment of experimental alcoholism

2019 ◽  
pp. 33-39
Author(s):  
П.К. Анохин ◽  
А.Г. Веретинская ◽  
Т.В. Давыдова ◽  
И.Ю. Шамакина
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Abuse ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Receptor Activation ◽  
Monoamine Oxidase A ◽  
Synaptic Proteins ◽  
Mesolimbic Dopamine ◽  
Dopamine D2 ◽  
Mao A

Введение. Стратегия активации дофаминовых D2 рецепторов их агонистами успешно используется в терапии таких дофамин-дефицитных состояний как болезнь Паркинсона и гиперпролактинемия. Дисфункция мезолимбической дофаминовой системы при алкогольной зависимости связана со снижением плотности D2 рецепторов в стриатуме, что делает их крайне интересными в качестве фармакологических мишеней новых лекарственных средств лечения алкоголизма. Цель исследования - проверка гипотезы о возможности применения агонистов D2 рецепторов для коррекции дисфункции дофаминовой мезолимбической системы и снижения потребления алкоголя у животных с экспериментальной алкогольной зависимостью. Методы. Эффект эрголинового агониста D2-рецепторов каберголина на добровольное потребление алкоголя изучали в экспериментальной модели «свободный выбор» у крыс-самцов Wistar. Содержание дофамина (DA) в среднем мозге и стриатуме определяли методом ВЭЖХ с электрохимической детекцией. Относительный уровень мРНК тирозингидроксилазы (ТН); дофамин-транспортного белка (DAT); моноаминоксидазы А (МАО А); синаптических белков SNAP25 и синаптобревина (VAMP2) изучали методом полимеразной цепной реакции в режиме реального времени после обратной транскрипции (ОТ-ПЦР). Результаты. При системном введении каберголина в дозе 0,5 мг/кг с интервалом 48 ч максимальный эффект препарата - снижение уровня потребления алкоголя - наблюдался в течение первых суток после инъекции. После однократного введения каберголина отмечалось восстановление сниженного содержания дофамина в стриатуме крыс с высоким уровнем потребления алкоголя, не связанное с увеличением экспрессии мРНК ТН, МАО А или DAT. В то же время введение каберголина приводило к повышению экспрессии мРНК синаптических белков SNAP25 и VAMP2, играющих важную роль в регуляции везикулярного пула дофамина в мезолимбической системе. Заключение. Полученные данные позволяют предположить, что стратегия активации дофаминовых D2-рецепторов их агонистами может быть эффективной для снижения потребления алкоголя, однако решение о целесообразности использования препаратов этой группы в терапии алкогольной зависимости требует дальнейшего изучения нейрохимических механизмов их действия и безопасности. Introduction. The strategy of dopamine D2 receptor activation has been successfully used in the therapy of dopamine-deficient states such as Parkinson’s disease and hyperprolactinemia. Mesolimbic dopamine «hypofunction» in alcohol addicts is closely associated with the reduction in striatal D2 receptor density making it an attractive pharmacological target for alcohol abuse therapy. The aim of this study was to test the hypothesis that D2 receptor agonists can be applied to correct dopamine mesolimbic dysfunction and reduce alcohol consumption in animals with experimental alcohol dependence. Methods. The effect of selective ergoline D2 agonist cabergoline on voluntary alcohol consumption was studied using “free choice” model in male Wistar rats. The dopamine (DA) content in the midbrain and striatum was determined by HPLC with electrochemical detection. The relative mRNA level of tyrosine hydroxylase (TH), dopamine transporter (DAT), monoamine oxidase A (MAO A), synaptic proteins SNAP25 and synaptobrevin (VAMP2) were studied by real-time polymerase chain reaction after reverse transcription (RT-PCR). Results. Systemic administration of cabergoline (0.5 mg/kg, every 48 hours) produced a decrease in alcohol consumption with the maximum effect observed during the first 24 h after injection. Acute injection of cabergoline restored a reduced DA level in the striatum of rats with high level of alcohol consumption, but this effect was not associated with an increase in the expression of TH, MAO A or DAT mRNA. At the same time, cabergoline increased mRNA expression of synaptic proteins SNAP25 and VAMP2, which play an important role in the regulation of the mesolimbic dopamine reserve vesicular pool. Conclusion. Our findings suggest that the strategy of dopamine D2 receptor activation may be effective in correction dopamine «hypofunction» and reducing alcohol consumption, however, to determine the feasibility of using D2 agonists in the treatment of alcohol abuse further study of their effectiveness, safety and neurochemical mechanisms of action are required.

Effect of amphetamine on dopamine D2 receptor binding in the primate brain with the agonist ligand [11C]MNPA

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S646-S646
Author(s):  
Nicholas Seneca ◽  
Sjoerd Finnema ◽  
Masanori Ichise ◽  
Balazs Gulyas ◽  
Håkan Wikstrom ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2 ◽  
Primate Brain
Sign in / Sign up

Export Citation Format

Share Document