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Fig. 1 · Structure
Cat. No.
A11360
CAS No.
184025-18-1
Formula
C16H18N2O2
Mol. Weight
270.3

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Ciproxifan

Cat. No. A11360 CAS 184025-18-1
Ciproxifan is an extremely potent histamine H3 inverse agonist/antagonist.

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Publications for Ciproxifan

1 publication citing this product

  1. K Yamamoto, .et al. , Naunyn-Schmiedeberg's Arch Pharmacol, 2019, pp 1-12 PMID: 30919010
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Biological Activity

Bioactivity / Mechanism

Ciproxifan binds histamine H3 receptors with species-dependent affinity. In parallel recombinant-receptor assays, its Ki was 3.9 ± 0.2 nM at rat H3 receptors and 46 ± 4 nM at human H3 receptors. These binding results support greater affinity at the rat receptor under the tested conditions. [1]

Ciproxifan also inhibits human and rat MAO A and MAO B in biochemical assays at micromolar concentrations. Human MAO inhibition recovered after dilution, supporting reversibility. This additional activity limits attribution of effects at high exposure exclusively to H3 receptors; in vivo MAO inhibition was not demonstrated in these experiments. [2]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
H3 receptor IC50 9.2 nM

In Vitro Studies

Species-dependent H3 receptor binding

Biochemical assay · Membranes of CHO-K1 cells stably expressing rat or human H3 receptors, approximately 300 fmol/mg protein [1]

Ciproxifan displaced [125I]-iodoproxyfan with greater affinity at rat than human H3 receptors. Reported Ki values are assay-derived binding endpoints.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Rat H3 receptor radioligand displacementKi 3.9 ± 0.2 nM; mean ± s.e.mean; 3 independent experiments with triplicate determinations[1]
Human H3 receptor radioligand displacementKi 46 ± 4 nM; mean ± s.e.mean; 3 independent experiments with triplicate determinations[1]

Literature-Reported Treatment Conditions

Exposure duration
60 min at 25°C
Method
Competing ciproxifan with 25 pM [125I]-iodoproxyfan; nonspecific binding defined with 1 μM imetit
Vehicle
50 mM phosphate binding buffer, pH 6.8
Reported limits
Ciproxifan solvent, salt designation and batch purity not specified in retrieved assay methods.
Methods and source locations

Compound reported in the paper: Ciproxifan

Binding affinity at the named recombinant receptors; does not establish functional inverse agonist potency or clinical efficacy.

Table 1; Results: Comparison of rH3R and hH3R pharmacological profiles in CHO cells; Methods: binding assays and analysis

Rat H3 receptor radioligand displacement: [125I]-iodoproxyfan displacement; Ki calculated from IC50 using ligand concentration and dissociation constant — Table 1, ciproxifan row and table footnote; Methods: binding assays and Analysis of data

Human H3 receptor radioligand displacement: Same-paper parallel human receptor binding assay — Table 1, ciproxifan row and table footnote

Human MAO inhibition and dilution validation

Biochemical assay · Human recombinant membrane-bound MAO A and MAO B [2]

Ciproxifan inhibited both human MAO isoforms at micromolar concentrations, with substrate-dependent MAO B IC50 values. Activity recovered after dilution, supporting reversible inhibition; l-deprenyl served as a persistent-inhibition comparator.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Human MAO A inhibition with kynuramineIC50 11.4 ± 1.2 μM (n = 5)[2]
Human MAO B inhibition with benzylamineIC50 4.3 ± 0.7 μM (n = 5)[2]
Human MAO B inhibition with kynuramineIC50 2.1 ± 0.3 μM (n = 9)[2]
Activity after ciproxifan preincubation and 100-fold dilutionResidual activity MAO A: 107.7 ± 3.4%; MAO B: 91.4 ± 9.7% of water-preincubated control; l-deprenyl MAO B comparator: 51.1 ± 2.9%[2]

Literature-Reported Treatment Conditions

Treatment concentration
10^-9 to 10^-3 M for concentration-response; 10 × IC50 for dilution validation
Exposure duration
Initial-rate measurements over at least 30 min at 30°C; validation preincubation 15 min at 30°C
Method
Spectrophotometric product formation; kynuramine for MAO A, kynuramine or benzylamine for MAO B
Vehicle
50 mM potassium phosphate, pH 7.4; water-preincubated control in dilution experiment
Reported limits
IC50 values are mean ± s.e.m. of n independent experiments, each at least in duplicate. Replication/error convention for the recovery percentages is not explicitly specified in the results sentence; no n inferred. SI not retrieved.
Methods and source locations

Compound reported in the paper: Ciproxifan

Biochemical off-target activity; these concentrations are not animal doses or proof of MAO inhibition in treated brain.

Results: human IC50 determination and reversibility; Table 2; Figure 1a; corresponding Methods

Human MAO A inhibition with kynuramine: Spectrophotometric initial-rate assay; substrate at 2 × KM — Table 2, ciproxifan row, hMAO A/KYN column and footnote

Human MAO B inhibition with benzylamine: Spectrophotometric initial-rate assay; substrate at 2 × KM — Table 2, ciproxifan row, hMAO B/BZA column and footnote

Human MAO B inhibition with kynuramine: Spectrophotometric initial-rate assay; substrate at 2 × KM — Table 2, ciproxifan row, hMAO B/KYN column and footnote

Activity after ciproxifan preincubation and 100-fold dilution: Preincubation at 10 × IC50, then 100-fold dilution; saturated substrate at 10 × KM — Results and Methods: Reversibility of human MAO inhibition

Rat brain MAO inhibition

Biochemical assay · Crude pooled brain homogenates from male Wistar rats; three brains per experimental preparation [2]

Ciproxifan inhibited rat brain MAO A and B in vitro at micromolar concentrations. This is an ex vivo enzyme preparation assay, not an animal dosing experiment.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Rat brain MAO A inhibition using serotoninIC50 37.5 ± 0.2 μM (n = 3)[2]
Rat brain MAO B inhibition using phenylethylamineIC50 15.4 ± 0.3 μM (n = 3)[2]

Literature-Reported Treatment Conditions

Treatment concentration
Six concentrations between 10^-9 M and 5 × 10^-4 M
Method
Radiometric substrate conversion in rat brain homogenates
Reported limits
Mean ± s.e.m.; three independent experiments, each in duplicate. Reaction duration and ciproxifan solvent not specified in retrieved radiometric Methods; no conditions borrowed from human assay.
Methods and source locations

Compound reported in the paper: Ciproxifan

Supports a possible off-target confound at sufficiently high exposure; does not demonstrate in vivo MAO inhibition or rat reversibility.

Table 2; Figure 1b; Methods and Results: IC50 determination for rat brain MAO

Rat brain MAO A inhibition using serotonin: Radiometric assay with 200 μM serotonin — Table 2, ciproxifan row, rMAO A/5-HT column; corresponding Methods

Rat brain MAO B inhibition using phenylethylamine: Radiometric assay with 20 μM phenylethylamine — Table 2, ciproxifan row, rMAO B/PEA column; corresponding Methods

In Vivo Studies

In male mice, acute ciproxifan increased wakefulness in wild-type animals but produced no significant wake response in H3-receptor knockout littermates. Paradoxical sleep amount showed no clear change in either genotype. The study used 1 mg/kg intraperitoneally on its reported compound (salt) weight basis; the specific counterion was not identified, so this is not a free-base dose equivalence for the catalog material. [3]

Acute wake response with H3-receptor knockout control

Animal study · Male H3R+/+ and H3R−/− littermate mice on C57BL/6J background; n = 10 per genotype; implanted at 12 weeks and 23–28 g [3]

Acute ciproxifan increased wake time and reduced slow-wave sleep in wild-type mice; the wake response was absent in H3-receptor knockout mice. Paradoxical sleep amount did not clearly change in either genotype.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Wake time during first 4 h in H3R+/+ miceWake time 126 ± 11 min with ciproxifan versus 80 ± 4 min with saline; mean ± SEM; n = 10; p < 0.001[3]
Wake time during first 4 h in H3R−/− miceWake time 77 ± 5 min with ciproxifan versus 73 ± 4 min with saline; mean ± SEM; n = 10; p > 0.05[3]

Conditions shared by the study groups

Route
Intraperitoneal
Frequency
Acute administration at 10 a.m.; at least 7 days between pharmacological injections
Treatment course
First 4 h after dosing analyzed for adopted outcome
Vehicle
0.1–0.3 mL saline
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
Wild-type H3R+/+
1 mg/kg, source-reported compound (salt) weight		Saline injection in the same animals; n = 10 per genotypeWake increased and SWS decreased; paradoxical sleep amount showed no clear change.[3]
H3R knockout H3R−/−
1 mg/kg, source-reported compound (salt) weight		Saline injection in the same animals; n = 10 per genotypeNo significant change in wake time or sleep latency; no clear change in paradoxical sleep amount.[3]
Wild-type H3R+/+
Model: Male wild-type littermate mice
Reported limits: Specific ciproxifan counterion not identified; no free-base dose conversion.
H3R knockout H3R−/−
Model: Male H3-receptor knockout littermate mice
Reported limits: Specific ciproxifan counterion not identified; no free-base dose conversion.
Methods and source locations

Compound reported in the paper: Ciproxifan

Qualitative genotype-dependent response to the reported material. Reported dose remains on the original weight basis; no Adooq free-base regimen or lot validation.

Methods: Animals, recording/scoring, pharmacological administration and statistical analysis; Results: Ciproxifan; Figure 7

Wake time during first 4 h in H3R+/+ mice: EEG/EMG-based sleep-wake scoring; Bonferroni tests following repeated-measures two-way ANOVA — Results: Drug Actions on the Sleep-Wake Cycle—Ciproxifan; Figure 7b

Wake time during first 4 h in H3R−/− mice: Same scoring and saline comparison; reported Bonferroni test — Results: Ciproxifan, knockout paragraph; Figure 7b

Wild-type H3R+/+ · Methods: pharmacological administration; Results: Ciproxifan; Figure 7b–c

H3R knockout H3R−/− · Methods: pharmacological administration; Results: Ciproxifan; Figure 7b–c

Specifications

Manufacturer Adooq Bioscience
Actions Inverse Agonist
CAS Number 184025-18-1
Formula C16H18N2O2
Molecular Weight 270.3
SMILES
C1CC1C(=O)C2=CC=C(C=C2)OCCCC3=CN=CN3

Storage & Solubility

In Vitro Solubility

Reported Solubility

No reported solubility data are available for this product.

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Ligneau X, Morisset S, Tardivel-Lacombe J, et al. Distinct pharmacology of rat and human histamine H(3) receptors: role of two amino acids in the third transmembrane domain. British journal of pharmacology (2000). PMID: 11090094 DOI: 10.1038/sj.bjp.0703712 Source material
  2. [2] Hagenow S, Stasiak A, Ramsay RR, et al. Ciproxifan, a histamine H3 receptor antagonist, reversibly inhibits monoamine oxidase A and B. Scientific reports (2017). PMID: 28084411 DOI: 10.1038/srep40541 Source material
  3. [3] Gondard E, Anaclet C, Akaoka H, et al. Enhanced histaminergic neurotransmission and sleep-wake alterations, a study in histamine H3-receptor knock-out mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2013). PMID: 23303066 DOI: 10.1038/npp.2012.266 Source material

Publications

1 publication citing this product

  1. K Yamamoto, .et al. , Naunyn-Schmiedeberg's Arch Pharmacol, 2019, pp 1-12 PMID: 30919010

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