SR 48692

Names

[ Name ]:
SR 48692

[Synonym ]:
Reminertant
merclinertant
SR48692
2-({[1-(7-Chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)adamantane-2-carboxylic acid
UNII-5JBP4SI96H
2-({[1-(7-Chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)-2-adamantanecarboxylic acid
Meclinertant
Tricyclo[3.3.1.1]decane-2-carboxylic acid, 2-[[[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)-1H-pyrazol-3-yl]carbonyl]amino]-

Biological Activity

[Description]:

Meclinertant (SR 48692) is a potent, selective, nonpeptide and orally active neurotensin receptor 1 (NTS1) antagonist. In human colon carcinoma (HT-29) cells, Meclinertant competitively antagonizes neurotensin-induced intracellular Ca2+ mobilization with a pA2 values of 8.13. Meclinertant has anxiolytic, anti-addictive and memory-impairing effects[1][2][3].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Neurotensin Receptor

Research Areas >> Neurological Disease

[Target]

Neurotensin receptor 1 (NTS1)[1]

[In Vitro]

In vitro, Meclinertant (SR 48692) competitively inhibits 125I-labeled neurotensin binding to the high-affinity binding site present in brain tissue from various species with IC50 values of 0.99 nM (guinea pig), 4.0 nM (rat mesencephalic cells), 7.6 nM (COS-7 cells transfected with the cloned high-affinity rat brain receptor), 13.7 nM (newborn mouse brain), 17.8 nM (newborn human brain), 8.7 nM (adult human brain), and 30.3 nM (HT-29 cells). Meclinertant also displaces 125I-labeled neurotensin from the low-affinity levocabastine-sensitive binding sites but at higher concentrations (34.8 nM for adult mouse brain and 82.0 nM for adult rat brain)[1]. In guinea pig striatal slices, Meclinertant blocks K+-evoked release of [3H]dopamine stimulated by neurotensin with a potency (IC50 = 0.46 nM) that correlates with its binding affinity[1].

[In Vivo]

Meclinertant (SR 48692) treatment reverses at 80 μg/kg the turning behavior induced by intrastriatal injection of neurotensin in mice and with a long duration of action (6 hours)[1].

[References]

[1]. Gully D, et al. Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):65-9.

[2]. Griebel G, et al. Characterization of the profile of neurokinin-2 and neurotensin receptor antagonists in the mouse defense test battery. Neurosci Biobehav Rev. 2001 Dec;25(7-8):619-26.

[3]. Felszeghy K, et al. Neurotensin receptor antagonist administered during cocaine withdrawal decreases locomotor sensitization and conditioned place preference. Neuropsychopharmacology. 2007 Dec;32(12):2601-10.

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
781.2±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C₃₂H₃₁ClN₄O₅

[ Molecular Weight ]:
587.065

[ Flash Point ]:
426.2±32.9 °C

[ Exact Mass ]:
586.198303

[ PSA ]:
119.06000

[ LogP ]:
4.55

[ Vapour Pressure ]:
0.0±2.8 mmHg at 25°C

[ Index of Refraction ]:
1.729

[ Storage condition ]:
-20°C

MSDS

Click to get detail MSDS

Safety Information

[ RTECS ]:
YD1988500

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Neurotensin in the ventral pallidum increases extracellular gamma-aminobutyric acid and differentially affects cue- and cocaine-primed reinstatement.

J. Pharmacol. Exp. Ther. 325(2) , 556-66, (2008)

Cocaine-primed reinstatement is an animal model of drug relapse. The neurocircuitry underlying cocaine-primed reinstatement includes a decrease in GABA in the ventral pallidum (VP) that is inhibited b...

Hypothalamic neurotensin projections promote reward by enhancing glutamate transmission in the VTA.

J. Neurosci. 33(18) , 7618-26, (2013)

The lateral hypothalamus (LH) sends a dense glutamatergic and peptidergic projection to dopamine neurons in the ventral tegmental area (VTA), a cell group known to promote reinforcement and aspects of...

The role of neurotensin in positive reinforcement in the rat central nucleus of amygdala.

Behav. Brain Res. 208(2) , 430-5, (2010)

In the central nervous system neurotensin (NT) acts as a neurotransmitter and neuromodulator. It was shown that NT has positive reinforcing effects after its direct microinjection into the ventral teg...