GR-103545
From Wikipedia, the free encyclopedia
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| Names | |
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| IUPAC name
methyl (3R)-4-[2-(3,4-dichlorophenyl)acetyl]-3-(pyrrolidin-1-ylmethyl)piperazine-1-carboxylate | |
| Other names
GR-103545; 860VEX6583; GR103545 | |
| Identifiers | |
3D model (JSmol) |
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| ChEMBL | |
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PubChem CID |
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| Properties | |
| C19H25Cl2N3O3 | |
| Molar mass | 414.3 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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GR-103545 is a potent and highly selective κ-opioid receptor (KOR) agonist primarily employed as a radioligand in positron emission tomography (PET) neuroimaging research.[1][2][3] When radiolabeled with carbon-11, [11C]GR-103545 serves as a neuroimaging tracer for quantifying KOR availability and receptor occupancy in the human brain.[1]
Mechanism of action
GR-103545 acts as an agonist of the κ-opioid receptor (KOR), exhibiting high selectivity over other opioid receptor subtypes.[1] The compound represents the active (−)-enantiomer of the racemic mixture GR-89696.[3]
Binding affinity and selectivity
Based on In vitro radioligand competition assays using recombinant cells expressing human opioid receptors GR-103545 binds to KOR with high affinity (Ki = 0.02 ± 0.01 nmol/L) and exhibits substantial selectivity over μ-opioid receptors (Ki = 16 ± 5 nmol/L) and δ-opioid receptors (Ki = 536 ± 234 nmol/L).[1] It is approximately 800-fold selective for KOR over μ-opioid and even more selective over δ-opioid receptors.[1] The in vivo dissociation constant (KD) of [11C]GR-103545 has been estimated at 0.069 nmol/L in humans and 0.048 nmol/L in rhesus macaques.[1][2][4]
Regional distribution
The highest binding potential values based on [11C] radioligand are observed in the amygdala, anterior cingulate cortex, and insula.[1][3] Intermediate binding is detected in the temporal lobe, frontal lobe, globus pallidus, and putamen, while lower binding is observed in the occipital lobe, caudate nucleus, hippocampus, posterior cingulate cortex, cerebellum, and thalamus.[1][2][3] In titi monkeys the highest binding was observed in the pituitary gland, followed by the insula, claustrum, and orbitofrontal cortex.[2]