184025-18-1

Ciproxifan是一种高效的，选择性的histamin H3-receptor拮抗剂，IC50为9.2 nM，作用于其他受体亚型具有低亲和力。

Ciproxifan inhibits [³H]HA release from synaptosomes with K_i of 0.5 nM. Ciproxifan inhibits the binding of [¹²⁵I]iodoproxyfan at the brain H3 receptor with K_i 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 α_1D and β₁, serotonin 5-HT_1B, 5-HT_2A, 5-HT₃ and 5-HT₄).

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. Ciproxifan (10 mg/kg i.p.) enhances prepulse inhibition in the DBA/2 strain mice. Ciproxifan (3 mg/kg i.p.) alleviates hyperactivity and cognitive deficits in the APP Tg2576 mouse model of Alzheimer's disease. Ciproxifan (3 mg/kg i.p.) improves accuracy and decreased impulsivity in adult male hooded Lister rats.

H 3 receptor 9.2 nM (IC 50 )