iproxifan maleate (FUB 359 maleate) is a potent, selective, orally bioavailable, and competitive antagonist of the histamine H3 receptor, demonstrating an IC50 of 9.2 nM. It exhibits low apparent affinity at other receptor subtypes and is applicable for research into aging disorders and Alzheimer's disease [1][3].
体内研究
A single oral dose of Ciproxifan (1 mg/kg) increases t-MeHA levels in the mouse brain, with an ED50 of 0.14 mg/kg [1].
When administered intraperitoneally at 3 mg/kg, Ciproxifan enhances the accuracy of responding in the five-choice task in rats but only when the stimulus duration is 0.25 sec instead of 0.50 sec [1].
Oral administration of Ciproxifan at doses ranging from 0.15 to 2 mg/kg induces significant signs of neocortical electroencephalogram activation, characterized by enhanced fast-rhythms density and an almost complete waking state in cats [1].
Following a single intravenous dose of 1 mg/kg, Ciproxifan reduces H3-receptor ligand concentration in the serum in mice, with half-lives (t1/2) of 13 and 87 min for the distribution and elimination phases, respectively [1].
A single oral dose of Ciproxifan at 1 mg/kg demonstrates oral bioavailability (F=62%) and reaches maximal concentration (Cmax=420 nM) in mice [1].
体外研究
Ciproxifan inhibits [3H]HA release from synaptosomes of the rat cerebral cortex, with a Ki of 0.5 nM [1].
At concentrations ranging from 0.01 nM to 1 μM for 60 minutes, Ciproxifan inhibits the binding of [125I].iodoproxyfan with rat striatal membranes, with a Ki of 0.7 nM [1].
Ciproxifan maleate 细胞实验
Cell Line
Concentration
Treated Time
Description
References
H1975 cells
10–80μM
48 h
inhibited cell growth and induced apoptosis
Acta Pharmacol Sin. 2021 Aug;42(8):1288-1297.
H460 cells
10–80μM
48 h
inhibited cell growth and induced apoptosis
Acta Pharmacol Sin. 2021 Aug;42(8):1288-1297.
A549 cells
10–80μM
48 h
inhibited cell growth and induced apoptosis
Acta Pharmacol Sin. 2021 Aug;42(8):1288-1297.
Ciproxifan maleate 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
H1975 cell xenograft model
Intraperitoneal injection
3 mg/kg
Every other day
Significantly inhibited tumor growth
Acta Pharmacol Sin. 2021 Aug;42(8):1288-1297.
Mice
H1R knockout mice
Intraperitoneal injection
0.3, 1, or 3 mg/kg
Single dose, observed for 24 hours
To investigate the effect of the H3R antagonist ciproxifan on wakefulness in WT and H1R KO mice. Results showed that ciproxifan dose-dependently increased wakefulness in WT mice but had no effect in H1R KO mice.
Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4687-92
Rat
Gastric mucosal injury model
Intragastric administration
3 mg/kg
Single dose, administered 30 minutes prior
To investigate the effect of Ciproxifan on (R)-α-methylhistamine-induced gastric mucosal cell proliferation and migration. Results showed that Ciproxifan reversed the (R)-α-methylhistamine-induced proliferation and accelerated migration.
Br J Pharmacol. 2002 Sep;137(2):237-44
Rat
HCl-induced gastric mucosal lesion model
Intragastric administration
0.3, 1 and 3 mg/kg
Single dose, 30 minutes before (R)-a-methylhistamine, followed by HCl 30 minutes later
To investigate the inhibitory effect of ciproxifan on the gastroprotective action of (R)-a-methylhistamine. Results showed that ciproxifan dose-dependently inhibited the protection exerted by (R)-a-methylhistamine, with the highest dose almost completely reversing the protective effect.
Br J Pharmacol. 2000 Apr;129(8):1597-600
Mice
H3R knockout mice and wild-type C57BL/6J mice
Intraperitoneal injection
0.3, 1, or 3 mg/kg
Single administration, 30 minutes before DID experiment
To investigate the effect of H3R antagonist ciproxifan on alcohol intake in mice. Results showed that ciproxifan significantly reduced alcohol consumption but had no effect on sucrose intake.
Neuropsychopharmacology. 2011 Sep;36(10):2030-40
Mice
C57Bl/6J male mice
Intraperitoneal injection
3 mg/kg
Single dose, 30 minutes before testing
To investigate the effects of ciproxifan on contextual memory retrieval in mice under stress and non-stress conditions. Results showed that ciproxifan enhanced memory retrieval of D2 in non-stress condition and of D1 in stress condition. Additionally, ciproxifan mitigated the stress-induced increase in Fos expression in the prelimbic and infralimbic cortex, central and basolateral amygdala, and the CA1 region of the dorsal hippocampus.
CNS Neurosci Ther. 2019 Aug;25(8):832-841
Adult male Long-Evans rats
MK-801-induced behavioral dysfunction model
Subcutaneous injection
1.0 and 3.0 mg/kg
Single administration, 20 minutes before testing
Ciproxifan enhanced the effects of MK-801 on locomotor activity and ataxia, but did not alter the changes in auditory startle and PPI induced by MK-801. Additionally, ciproxifan alleviated the impairment of delayed spatial alternation caused by MK-801.
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