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]. IC50 & 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].