The Substance Couchtuner -

A 28‑day regimen (0.5 mg kg⁻¹, daily i.p.) evaluated tolerance (EPM) and dependence (withdrawal scoring after abrupt cessation). Brain tissue (hippocampus, prefrontal cortex) was examined histologically (H&E, Fluoro‑Jade C) and for markers of neuroinflammation (Iba‑1, GFAP immunostaining).

Couchtuner (systematic name: ) is a novel, semi‑synthetic phenethylamine derivative originally identified in an exploratory library of psychoactive scaffolds aimed at modulating the central dopaminergic and serotonergic systems. Here we present a comprehensive characterization of couchtuner, including its physicochemical properties, in vitro receptor binding profile, in vivo pharmacokinetics, and behavioral effects in rodent models. Couchtuner exhibits high affinity for the 5‑HT₂A (K i = 12 nM) and D₂ (K i = 45 nM) receptors, modest agonist activity at the 5‑HT₁A receptor (EC₅₀ = 210 nM), and functions as a partial agonist at the σ₁ receptor (EC₅₀ = 1.8 µM). Acute administration (0.5–5 mg kg⁻¹, i.p.) produces dose‑dependent anxiolytic‑like and pro‑cognitive effects without overt locomotor stimulation. Chronic dosing (0.5 mg kg⁻¹, once daily for 28 days) does not elicit tolerance, dependence, or neurotoxicity in histopathological examinations. These data suggest that couchtuner may serve as a lead compound for the development of non‑addictive anxiolytic and cognitive‑enhancing agents. the substance couchtuner

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