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Updated: May 26, 2026

Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
Published on: August 10, 2012
Selective agonists for dopamine/neurotensin receptor heterodimers
Susanne Koschatzky1, Peter Gmeiner
1Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich Alexander University, Schuhstr. 19, 91052 Erlangen, Germany.
Abstract:
The neuromodulatory peptide neurotensin has been described to functionally interact with dopaminergic pathways of the human brain. We employed radioligand binding studies to investigate the physical interaction between co-expressed dopamine D(2L) or D₃ and neurotensin NTS₁ or NTS₂ receptors. Substantial cross-inhibitory effects of both receptor subtypes NTS(1) and NTS₂ on the agonist binding of D(2L) or D₃ were detected in the presence of neurotensin. To identify ligand-specific modulation and subtype-dependent differences, the novel dopamine receptor agonists 5 and 6 bearing the 7-OH-DPAT pharmacophore were synthesized. Exceptional ligand specificity was observed for D₃-NTS₂ co-expression, which gave a 20-fold decrease in affinity for biphenylcarboxamide 5 in the presence of neurotensin. Comparing the binding properties of dopaminergic compounds in the presence of neurotensin, dopamine receptor subtype-selective profiles of the cross-inhibitory effect of neurotensin were observed.
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