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The first total synthesis of (+)-7-bromotrypargine, a β-carboline alkaloid from Ancornia sp. is reported. The synthesis proceeds in 9 steps, 8 steps longest linear sequence, in 36.9% overall yield. Biological characterization found that (+)-7-bromotrypargine is an H(3) antagonist, and a selective inhibitor of DAT and NET, without inhibiting SERT. Moreover, unlike electron rich congeners, (+)-7-...

Photoaffinity labeling, a useful in vivo biochemical tool, is limited when applied in vivo because of the poor tissue penetration by ultraviolet (UV) photons. This study investigates affinity labeling using tissue-penetrating radiation to overcome the tissue attenuation and irreversibly label membrane receptor proteins. Using X-ray (115 kVp) at low doses (<50 cGy or Rad), specific and irreversi...

The molecular mechanisms generating the mania-like abnormal behaviors caused by diacylglycerol (DG) kinase (DGK) η deficiency remain unclear. Here, we found that DGKη knockout markedly increased dopamine (DA) levels in midbrain (DA-producing region, 2.8-fold) and cerebral cortex (DA projection 1.2-fold). Moreover, significantly augmented phosphorylated DA transporter (DAT) (1.4-fold increase), ...

In this paper we explore the strengths and gaps among NGO surveys based on an analysis of the records held in the CE-DAT database at CRED. We conclude by recommending the priority areas for strengthening NGO capacity to undertake surveys and ways to improve data quality in general.

The plasma membrane monoamine transporter (PMAT) and organic cation transporter 3 (OCT3) are the two most prominent low-affinity, high-capacity (i.e., uptake(2)) transporters for endogenous biogenic amines. Using the Flp-in system, we expressed human PMAT (hPMAT) and human OCT3 (hOCT3) at similar levels in human embryonic kidney 293 cells. Parallel and detailed kinetics analysis revealed distin...

Despite intensive medication development efforts, no effective pharmacotherapy for cocaine abuse has demonstrated efficacy for long-term use. Given the obvious importance of the dopamine transporter in the addictive properties of cocaine, the development and use of compounds that target the dopamine transporter represents a reasonable approach for the pharmacological treatment of cocaine abuse....

Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET). Cocaine reward/reinforcement has been linked to actions at DAT or to blockade of SERT. However, knockouts of neither DAT, SERT, or NET reduce cocaine reward/reinforcement, leaving substantial uncertainty about cocaine's molecular mechanisms for reward. Conceivably, the ...

Monoamine transporters, such as the dopamine transporter, 5-HT transporter and noradrenaline transporter, in the plasma membrane provide effective control over the intensity of monoamine-mediated signaling by recapturing neurotransmitters released by presynaptic neurons. These proteins represent established targets for several psychotropic drugs, including psychostimulants and antidepressants; ...