2-Bromo-LSD

2-Bromo-LSD (BOL-148) is a blood-brain barrier-permeable 5-HT_2A partial agonist and competitive partial antagonist. 2-Bromo-LSD acts as both a potent partial agonist (with an EC₅₀ of 0.81 nM for Gq dissociation) and a potent partial antagonist (with a K_B of 0.18 nM for Gq dissociation) at the 5-HT_2A receptor. 2-Bromo-LSD exhibits partial agonist activity at multiple aminergic GPCRs, including 5-HT_2A. 2-Bromo-LSD lacks 5-HT_2B agonist activity. 2-Bromo-LSD induces dendritogenesis and spinogenesis. 2-Bromo-LSD reverses the behavioral effects of chronic stress and increases active coping behaviors in mice^[1][2]. In Vitro:2-Bromo-LSD acts as both a potent partial agonist (EC₅₀ = 0.81 nM, Eₘₐₓ = 59.8% for Gq dissociation) and a potent partial antagonist (K_B = 0.18 nM for Gq dissociation) at the 5-HT₂A receptor^[2].
2-Bromo-LSD exerts weak blocking effects on hERG channels (IC₅₀ = 31.6 μM)^[2].
2-Bromo-LSD (1-10 μM; 3 h) promotes dendrogenesis and dendritic spine density in primary rat cortical neurons^[2]. In Vivo:2-Bromo-LSD (0.125-4 mg/kg; i.p.) dose-dependently increases striatal DOPA accumulation in rats, with maximum effects at 2-4 mg/kg that exceed those of equimolar LSD, acts as an antagonist of Apomorphine (HY-12723)-induced DOPA accumulation reduction, and blocks LSD's inhibitory effect on GBL-stimulated DOPA accumulation^[1].
2-Bromo-LSD (0.125-2.0 mg/kg; i.p.) co-administered with LSD does not produce a statistically significant change in striatal DOPA accumulation compared to 2-Bromo-LSD alone at matching doses^[1].
2-Bromo-LSD (0.1-10 mg/kg; i.p.; single dose) does not induce the hallucinogen-associated head-twitch response in male C57BL/6J mice, but dose-dependently blocks DOI-induced head-twitch responses, achieving 76% inhibition at the 3 mg/kg dose^[2].