ChEBI: Cyclopropyl-[4-[3-(1H-imidazol-5-yl)propoxy]phenyl]methanone is an aromatic ketone.
ciproxifan is a novel and potent antagonist of histamine h3-receptor with a ic50 value of 9.2±1.8nm [1].ciproxifan has shown the in-vitro antagonistic action to h3-receptor with a ic50 value of 9.2±1.8nm. in addition, ciproxifan has been reported to competitively antagonize the (r) α-meha induced relaxation of electrically stimulated guinea pig ileum longitudinal muscle. besides, ciproxifan has been revealed to have the effect on [125i]iodoproxyfan binding with a ki value of 0.7±0.2 nm. apart from these, ciproxifan has been found to be a selective antagonist with pki values of 9.3, 4.9, 4.6, 5.5, 5.4, 4.9, <5.0, 4.8, <5.5 and <5.7 for h3, h2, h1, muscarinic m3, adrenergic α1d, β1, serotonin 5-ht1b, 5-ht2a, 5-ht3 and 5-ht4, respectively [1].
Ciproxifan inhibits [3H]HA release from synaptosomes with Ki of 0.5 nM. It inhibits the binding of [125I]iodoproxyfan at the brain H3 receptor with Ki of 0.7 nM. It 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 >).
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 13 min and elimination phase of 87 min, respectively. Ciproxifan (1 mg/kg, po) 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. It 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. It (3 mg/kg, ip) significantly increased choice accuracy as evaluated in the five-choice task performed using a short stimulus duration. Ciproxifan (0.15-2 mg/kg, po) 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 ip) enhances prepulse inhibition in the DBA/2 strain mice. It (3 mg/kg ip) alleviates hyperactivity and cognitive deficits in the APP Tg2576 mouse model of Alzheimer's disease. Ciproxifan (3 mg/kg ip) improves accuracy and decreased impulsivity in adult male hooded Lister rats.
[1] ligneau x1, lin j, vanni-mercier g, jouvet m, muir jl, ganellin cr, stark h, elz s, schunack w, schwartz j. neurochemical and behavioral effects of ciproxifan, a potent histamine h3-receptor antagonist. j pharmacol exp ther. 1998 nov; 287(2):658-66.
