IHCH-7086 is a blood-brain barrier-permeable, partial β-arrestin-biased agonist of 5-HT 2A R with a K i of 12.59 nM. IHCH-7086 blocks D-lysergic acid diethylamide-induced head-twitch response in mice and alleviates depression-like behaviors in mice subjected to acute restraint stress or injected with Corticosterone. IHCH-7086 is applicable to research related to depression [1] [2].
In Vivo, IHCH-7086 (2-10 mg/kg; single administration) does not induce hallucination-like head twitch responses in mice at doses up to 10 mg/kg, but blocks LSD-induced head twitch responses at 10 mg/kg[2]. IHCH-7086 (10 mg/kg; i.p.; single acute administration) produces significant antidepressant-like effects in acute restraint stress-induced depression-like mice, as measured by reduced immobility in the TST and FST, with efficacy dependent on 5-HT2A receptor activation[2].
In Vitro, IHCH-7086 binds exclusively to the EBP of purified 5-HT2A R and exhibits a significant preference for activating β-arrestin signaling[1]. IHCH-7086 (multiple concentrations) acts as a β-arrestin-biased partial agonist at human 5-HT2AR, with a binding affinity of 12.59 nM, and does not activate Gq-mediated signaling[2].
References:
[1]. Yin YN, et al. Non-hallucinogenic Psychedelic Analog Design: A Promising Direction for Depression Treatment. Neurosci Bull. 2023 Jan;39(1):170-172.
[2]. Cao D, et al. Structure-based discovery of nonhallucinogenic psychedelic analogs. Science. 2022;375(6579):403-411.
In Vivo, IHCH-7086 (2-10 mg/kg; single administration) does not induce hallucination-like head twitch responses in mice at doses up to 10 mg/kg, but blocks LSD-induced head twitch responses at 10 mg/kg[2]. IHCH-7086 (10 mg/kg; i.p.; single acute administration) produces significant antidepressant-like effects in acute restraint stress-induced depression-like mice, as measured by reduced immobility in the TST and FST, with efficacy dependent on 5-HT2A receptor activation[2].
In Vitro, IHCH-7086 binds exclusively to the EBP of purified 5-HT2A R and exhibits a significant preference for activating β-arrestin signaling[1]. IHCH-7086 (multiple concentrations) acts as a β-arrestin-biased partial agonist at human 5-HT2AR, with a binding affinity of 12.59 nM, and does not activate Gq-mediated signaling[2].
References:
[1]. Yin YN, et al. Non-hallucinogenic Psychedelic Analog Design: A Promising Direction for Depression Treatment. Neurosci Bull. 2023 Jan;39(1):170-172.
[2]. Cao D, et al. Structure-based discovery of nonhallucinogenic psychedelic analogs. Science. 2022;375(6579):403-411.