Ciproxifan maleate (FUB 359)(FUB-359 maleate) is a highly potent and selective histamin H3-receptor antagonist with IC50 of 9.2 nM, with low apparent affinity at other receptor subtypes.

H3 receptor:9.2 nM

Ciproxifan inhibits [3H]HA release from synaptosomes with Ki of 0.5 nM. Ciproxifan inhibits the binding of [125I]iodoproxyfan at the brain H3 receptor with Ki of 0.7 nM. Ciproxifan displays high affinity at H3 receptor but shows low apparent affinity at other receptor subtypes as evaluated in functional tests on isolated organs (histamine H1 and H2, muscarinic M3, adrenergic α1D and β1, serotonin 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4). [1]

Ciproxifan intravenously injected at dose of 1 mg/kg decreases the H3-receptor ligand concentration in serum in Male Swiss mice, with half-times of distribution phase of 13min and elimination phase of 87 min, respectively. Ciproxifan (1 mg/kg, p.o.) rises brain t-MeHA level rapidly in Male Swiss mice, being already significantly increased after 30 min, reaching a plateau between 90 and 180 min and still remaining enhanced after 270 min. Ciproxifan leads to ED50 values of 0.23 mg/kg in cerebral cortex, 0.28 mg/kg in striatum and 0.30 mg/kg in hypothalamus in Male Wistar rats. Ciproxifan (3 mg/kg, i.p.) significantly increases choice accuracy as evaluated in the five-choice task performed using a short stimulus duration. Ciproxifan (0.15-2 mg/kg, p.o.) induces marked signs of neocortical electroencephalogram activation manifested by enhanced fast-rhythms density and an almost total waking state in cats. [1] Ciproxifan (10 mg/kg i.p.) enhances prepulse inhibition in the DBA/2 strain mice. [3] Ciproxifan (3 mg/kg i.p.) alleviates hyperactivity and cognitive deficits in the APP Tg2576 mouse model of Alzheimer's disease. [4] Ciproxifan (3 mg/kg i.p.) improves accuracy and decreased impulsivity in adult male hooded Lister rats. [5]