Definition
ChEBI: Cyclopropyl-[4-[3-(1H-imidazol-5-yl)propoxy]phenyl]methanone is an aromatic ketone.
Biological Activity
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].
in vitro
Ciproxifan inhibits [
3H]HA release from synaptosomes with K
i of 0.5 nM. It inhibits the binding of [
125I]iodoproxyfan at the brain H3 receptor with K
i of 0.7 nM. It 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-HT1B, 5-HT2A, 5-HT3 and 5-HT4 >).
in vivo
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 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.
References
[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.
