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Vesicular Glutamate Transporter Inhibitors: Structurally Modified Brilliant Yellow Analogs

Vesicular Glutamate Transporter Inhibitors: Structurally Modified Brilliant Yellow Analogs

Jason Kehrl, J Christian Althaus, Hollis D Showalter, DiAndra M Rudzinski, Michael A Sutton, Tetsufumi Ueda

Neurochem Res. 2017 Jun;42(6):1823-1832.

PMID: 28255754

Abstract:

Glutamate uptake into synaptic vesicles in nerve terminals is a pivotal step in glutamate synaptic transmission. Glutamate is the major excitatory neurotransmitter and, as such, the vesicular glutamate transporter (VGLUT) responsible for this uptake is involved in a variety of nervous system functions and various types of pathophysiology. As yet, no VGLUT-specific, membrane-permeable agents have been developed to affect neuronal function in intact neurons, although two potent VGLUTspecific inhibitors are known. These compounds contain diazo and highly charged sulfonic acid groups, rendering them membrane-impermeable and potentially cytotoxic. In an effort to eliminate these undesirable properties, we have developed two novel agents, Brilliant Yellow analogs 1 and 2, which are free of these two groups. We show here that these agents retain highly VGLUT-selective inhibitory activity, despite their reduction in potency, and exhibit no significant cellular toxicity. Potential use of this molecular modification is discussed.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP3051114	Brilliant Yellow		3051-11-4	Price

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