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 H
3 receptor but shows low apparent affinity at other receptor subtypes as evaluated in functional tests on isolated organs (histamine H
1 and H
2, muscarinic M
3, adrenergic α
1D and β
1, serotonin 5-HT
1B, 5-HT
2A, 5-HT
3 and 5-HT
4).
Ciproxifan intravenously injected at dose of 1 mg/kg decreases the H
3-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
)
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