English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Previous studies identified partial inhibitors and allosteric modulators of 5-hydroxytryptamine ([5-amino-3-(3,4-dichlorophenyl)-1,2-dihydropyrido[3,4-b]pyrazin-7-yl]carbamic acid ethyl ester [SoRI-6238], 4-(2-[bis(4-fluorophenyl)methoxy]ethyl)-1-(2-trifluoromethyl-benzyl)-piperidine [TB-1-099]) and dopamine transporters N-(diphenylmethyl)-2-phenyl-4-quinazolinamine, [SoRI-9804]). We report here the identification of three novel allosteric modulators of the dopamine transporter [N-(2,2-diphenylethyl)-2-phenyl-4-quinazolinamine [SoRI-20040], N-(3,3-diphenylpropyl)-2-phenyl-4-quinazolinamine [SoRI-20041], and [4-amino-6-[(diphenylmethyl)amino]-5-nitro-2-pyridinyl]carbamic acid ethyl ester [SoRI-2827]]. Membranes were prepared from human embryonic kidney cells expressing the cloned human dopamine transporter (hDAT). [(125)I]3beta-(4'-Iodophenyl)tropan-2beta-carboxylic acid methyl ester ([(125)I]RTI-55) binding and other assays followed published procedures. SoRI-20040, SoRI-20041, and SoRI-2827 partially inhibited [(125)I]RTI-55 binding, with EC(50) values ranging from approximately 1.4 to 3 microM and E(max) values decreasing as the [(125)I]RTI-55 concentrations increased. All three compounds decreased the [(125)I]RTI-55 B(max) value and increased the apparent K(d) value in a manner well described by a sigmoid dose-response curve. In dissociation rate experiments, SoRI-20040 (10 microM) and SoRI-20041 (10 microM), but not SoRI-2827 (10 microM), slowed the dissociation of [(125)I]RTI-55 from hDAT by approximately 30%. Using rat brain synaptosomes, all three agents partially inhibited [(3)H]dopamine uptake, with EC(50) values ranging from 1.8 to 3.1 microM and decreased the V(max) value in a dose-dependent manner. SoRI-9804 and SoRI-20040 partially inhibited amphetamine-induced dopamine transporter-mediated release of [(3)H]1-methyl-4-phenylpyridinium ion from rat caudate synaptosomes in a dose-dependent manner. Viewed collectively, we report several compounds that allosterically modulate hDAT binding and function, and we identify novel partial inhibitors of amphetamine-induced dopamine release.

Studies of the Biogenic Amine Transporters. 12. Identification of Novel Partial Inhibitors of Amphetamine-Induced Dopamine Release