更新于：2024-11-01

D2 receptor x MATs

更新于：2024-11-01

基本信息

关联

项与 D2 receptor x MATs 相关的药物

Amitriptyline hydrochloride/Perphenazine

盐酸阿米替林/奋乃静

靶点

D2 receptor x MATs

作用机制

D2 receptor拮抗剂 [+1]

在研机构-

原研机构-

在研适应症-

非在研适应症

焦虑症

最高研发阶段撤市

首次获批国家/地区

美国

首次获批日期1965-08-23

100 项与 D2 receptor x MATs 相关的临床结果

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100 项与 D2 receptor x MATs 相关的转化医学

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0 项与 D2 receptor x MATs 相关的专利（医药）

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项与 D2 receptor x MATs 相关的文献（医药）

2021-07-01·Biomolecules & Therapeutics3区 · 医学

Structural Requirements for Modulating 4-Benzylpiperidine Carboxamides from Serotonin/Norepinephrine Reuptake Inhibitors to Triple Reuptake Inhibitors

3区 · 医学

Article

作者: Min, Xiao ; Kim, Eunae ; Cheon, Seung Hoon ; Paudel, Suresh ; Kim, Kyeong-Man ; Zhu, Anlin ; Acharya, Srijan

8Kand a serotonin/norepinephrine reuptake inhibitor.7Jshowed that the regions spanning transmembrane domain (TM)1, TM3, and TM6 form the ligand binding pocket. The compound.8Kbound tightly to the binding pocket of all three monoamine reuptake transporters; however.7Jshowed poor docking with DAT. Co-expression of DAT with the dopamine D₂ receptor (D₂R) significantly inhibited DA-induced endocytosis of D₂R probably by reuptaking DA into the cells. Pretreatment of the cells with.8F, which is one of the compounds with good inhibitory activity on DAT, blocked DAT-induced inhibition of D₂R endocytosis. In summary, this study identified critical structural features contributing to the selectivity of a molecule for each of the monoamine transporters, critical residues on the compounds that bound to the transporters, and the functional role of a DA reuptake inhibitor in regulating D₂R function.

2020-08-01·Journal of Pharmacology and Experimental Therapeutics3区 · 医学

3,4-Methylenedioxypyrovalerone: Neuropharmacological Impact of a Designer Stimulant of Abuse on Monoamine Transporters

3区 · 医学

Article

作者: German, Christopher L ; Wilkins, Diana G ; Curtis, Peter S ; Anderson, David J ; Fleckenstein, Annette E ; Siripathane, Yasmeen H ; Hanson, Glen R ; Magee, Charlotte P

Methylenedioxypyrovalerone (MDPV) is an abused synthetic cathinone, commonly referred to as a "bath salt." Because the dopamine (DA) transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) are key regulators of both the abuse and neurotoxic potential of structurally and behaviorally related agents, the impact of MDPV on these transporters was investigated. Results revealed that a single in vivo MDPV administration rapidly (within 1 hour) and reversibly increased both rat striatal DAT and VMAT-2 activity, as assessed via [³H]DA uptake in synaptosomes and synaptic vesicles, respectively, prepared from treated rats. There was no evidence of an MDPV-induced increase in plasmalemmal membrane DAT surface expression. Plasma concentrations of MDPV increased dose-dependently as assessed 1 hour after 2.5 and 5.0 mg/kg (s.c.) administration and returned to levels less than 10 ng/ml by 18 hours after 2.5 mg/kg (s.c.). Neither pretreatment with a D1 receptor (SCH23390), a D2 receptor (eticlopride), nor a nicotinic receptor (mecamylamine) antagonist attenuated the MDPV-induced increase in DAT activity. In contrast, eticlopride pretreatment attenuated both the MDPV-induced increase in VMAT-2-mediated DA uptake and an associated increase in cytoplasmic-associated vesicle VMAT-2 immunoreactivity. SCH23390 did not attenuate the MDPV-induced increase in VMAT-2 activity. Repeated MDPV injections did not cause persistent DAergic deficits, as assessed 7 to 8 days later. The impact of MDPV on striatal and hippocampal serotonergic assessments was minimal. Taken together, these data contribute to a growing pharmacological rubric for evaluating the ever-growing list of designer cathinone-related stimulants. The profile of MDPV compared with related psychostimulants is discussed. SIGNIFICANCE STATEMENT: Pharmacological characterization of the synthetic cathinone, 3,4-methylenedioxypyrovalerone (MDPV; commonly referred to as a "bath salt"), is critical for understanding the abuse liability and neurotoxic potential of this and related agents. Accordingly, the impact of MDPV on monoaminergic neurons is described and compared with that of related psychostimulants.

2011-07-01·Psychopharmacology3区 · 医学

Neuroimaging and drug taking in primates

3区 · 医学

Review

作者: Leonard L. Howell ; Kevin S. Murnane

RATIONALENeuroimaging techniques have led to significant advances in our understanding of the neurobiology of drug taking and the treatment of drug addiction in humans. Neuroimaging approaches provide a powerful translational approach that can link findings from humans and laboratory animals.OBJECTIVEThis review describes the utility of neuroimaging toward understanding the neurobiological basis of drug taking and documents the close concordance that can be achieved among neuroimaging, neurochemical, and behavioral endpoints.RESULTSThe study of drug interactions with dopamine and serotonin transporters in vivo has identified pharmacological mechanisms of action associated with the abuse liability of stimulants. Neuroimaging has identified the extended limbic system, including the prefrontal cortex and anterior cingulate, as important neuronal circuitry that underlies drug taking. The ability to conduct within-subject longitudinal assessments of brain chemistry and neuronal function has enhanced our efforts to document long-term changes in dopamine D2 receptors, monoamine transporters, and prefrontal metabolism due to chronic drug exposure. Dysregulation of dopamine function and brain metabolic changes in areas involved in reward circuitry have been linked to drug taking behavior, cognitive impairment, and treatment response.CONCLUSIONSExperimental designs employing neuroimaging should consider well-documented determinants of drug taking, including pharmacokinetic considerations, subject history, and environmental variables. Methodological issues to consider include limited molecular probes, lack of neurochemical specificity in brain activation studies, and the potential influence of anesthetics in animal studies. Nevertheless, these integrative approaches should have important implications for understanding drug taking behavior and the treatment of drug addiction.