BP1.3656B

BP1.3656B is a selective, orally active, blood-brain barrier-permeable histamine H3 receptor ( histamine H3 receptor ) inverse agonist/antagonist, with a K B value of 0.08 nM for antagonizing agonist-induced activity and an IC₅₀ value of 0.38 nM for directly inhibiting the basal activity of the receptor. BP1.3656B reduces alcohol consumption, alcohol-seeking behavior, alcohol self-administration, motivation to drink, alcohol relapse, alcohol-induced hyperlocomotion, and binge alcohol intake. BP1.3656B is applicable for the research of alcohol use disorder ^[1].

In Vivo, BP1.3656B (0.003-1 mg/kg; p.o.; single administration) dose-dependently increases the level of t-MeHA in the brain of male OF1 mice, with an ED50 of 0.008 mg/kg^[1]. BP1.3656B (0.03-0.1 mg/kg; i.p.; single administration) dose-dependently increases extracellular acetylcholine levels in the hippocampus of male Wistar rats^[1]. BP1.3656B (0.005-0.3 mg/kg; single administration) reduces alcohol-induced motor hyperactivity in female DBA/2J mice^[1]. BP1.3656B (0.3 mg/kg; i.p.; once daily for 4 consecutive days) reduces alcohol-induced locomotor sensitization in female DBA/2J mice by 31%-44% over the 4-day treatment course^[1]. BP1.3656B (0.3 mg/kg; i.p.; single administration) reduces alcohol intake by 25% in male mice in the dark drinking model, normalizes anxiety-like behaviors in mice during alcohol withdrawal, and decreases voluntary alcohol intake in non-addicted and alcohol-dependent male rats^[1].

References:
[1]. Le Foll B, et al. Histamine H3 Receptor as a target for alcohol use disorder: challenging the predictability of animal models for clinical translation in drug development. Transl Psychiatry. 2026;16(1):55. Published 2026 Jan 29.