25CN-NBOH (hydrochloride)

25CN-NBOH hydrochloride exhibits agonist activity at the 5-HT_2a receptor, shows 90- to 100-fold selectivity over the 5-HT₂c receptor, and possesses blood-brain barrier permeability^[1][2][3]. 25CN-NBOH hydrochloride acts as an interoceptive agent with partial agonist-like properties^[1][2][3]. 25CN-NBOH hydrochloride serves as a pharmacological tool for 5-HT_2A receptor research, and its tritiated form functions as a selective agonist radioligand^[1]. 25CN-NBOH hydrochloride can be used to investigate diseases characterized by cognitive rigidity, schizophrenia, obsessive-compulsive disorder, depression, pain, inflammation, migraine, and cluster headache^[1][3]. In Vitro:25CN-NBOH hydrochloride (2 h) is a high-affinity ligand for human 5-HT_2AR (K_i = 1.7 nM). In a [³H]Cimbi-36 competitive binding assay using membranes from tsA201 cells transfected with human receptors, 25CN-NBOH shows 76-fold selectivity for human 5-HT_2AR over human 5-HT_2CR^[1].
25CN-NBOH hydrochloride (1 h) is a potent partial agonist of human 5-HT_2AR (EC₅₀ = 2.4 nM, achieving 77% of the maximal response induced by 5-HT), while acting as a full agonist of human 5-HT_2CR (EC₅₀ = 46 nM, achieving 119% of the maximal response induced by 5-HT), as determined by an IP-One HTRF assay using stable HEK293 cell lines^[1].
25CN-NBOH hydrochloride (30 min) is a potent partial agonist of human 5-HT_2AR (EC₅₀ = 0.41 nM, achieving 80% of the maximal effect of 5-HT). It also acts as a partial agonist of human 5-HT_2CR (EC₅₀ = 5.8 nM, achieving 56% of the maximal effect of 5-HT) in a Ca²⁺/Fluo-4 assay using stable HEK293 cell lines^[1].
25CN-NBOH hydrochloride exhibits high in vitro binding selectivity for 5-HT_2AR, with 52-100-fold higher affinity for 5-HT_2AR than for 5-HT_2CR, 37-fold higher affinity than for 5-HT_2BR, and acts as a potent agonist of 5-HT_2AR^[2].
25CN-NBOH hydrochloride shows 100-fold binding selectivity for human 5-HT_2AR over rat 5-HT_2CR, with a K_i value of 1.3 nM for human 5-HT_2AR and 132 nM for rat 5-HT_2CR^[3].
25CN-NBOH hydrochloride (30 min) is a potent agonist with 90-fold functional selectivity for human 5-HT_2AR over human 5-HT_2CR. The EC₅₀ values are 2.1 nM for human 5-HT_2AR and 190 nM for human 5-HT_2CR^[3]. In Vivo:25CN-NBOH (0.51 mg/kg; i.p.) hydrochloride induces head-twitch response in male C57BL/6J mice with an ED₅₀ of 1.45 μM/kg (95% CI 0.80-2.65 μM/kg)^[1].
25CN-NBOH (0.3-10 mg/kg; i.p.) hydrochloride reduces activity in female NMRI mice in an anxiety-related marble burying assay at doses of 0.3, 1, 3, and 10 mg/kg (i.p.)^[1].
25CN-NBOH (0.3-30 mg/kg; i.p.; single dose) hydrochloride induces 5-HT₂A receptor-mediated head twitch behavior in Mus musculus, with a maximal response of ~10 head twitches at 1.0 mg/kg, and dose-dependently attenuates DOI-elicited head twitches at doses ≥3.0 mg/kg^[2].
25CN-NBOH (0.1-30 mg/kg; i.p.; cumulative dose) hydrochloride produces partial 5-HT₂A receptor-mediated generalization to the DOI discriminative cue in mice, reaching a maximum of 55% DOI-appropriate responding at cumulative doses of 10.0 and 30.0 mg/kg^[2].
25CN-NBOH (0.1-30 mg/kg; i.p.; cumulative dose) hydrochloride does not generalize to the M100907 discriminative cue in mice, demonstrating no antagonist-like interoceptive effects at 5-HT₂A receptors^[2].