Premium
Selective Agonists for Dopamine/Neurotensin Receptor Heterodimers
Author(s) -
Koschatzky Susanne,
Gmeiner Peter
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100499
Subject(s) - neurotensin , neurotensin receptor , dopaminergic , agonist , dopamine , endogenous agonist , receptor , chemistry , pharmacology , dopamine receptor , radioligand , ligand (biochemistry) , medicine , endocrinology , biology , neuropeptide , biochemistry , dopamine receptor d1
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 D 3 and neurotensin NTS 1 or NTS 2 receptors. Substantial cross‐inhibitory effects of both receptor subtypes NTS 1 and NTS 2 on the agonist binding of D 2L or D 3 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 D 3 –NTS 2 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.