Cat. No.: HY-12199

Pitolisant

(Synonyms: Tiprolisant)

2 Cited Publications

Customer Review

Based on 2 publication(s) in Google Scholar

Pitolisant is a potent and selective nonimidazole inverse agonist at the recombinant human histamine H3 receptor (K_i=0.16 nM).

For research use only. We do not sell to patients.

Purity: 99.73%
CAS No.: 362665-56-3
Formula: C₁₇H₂₆ClNO
Molecular Weight:295.85

Storage:

Pure form -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Pitolisant Chemical Structure

CAS No.: 362665-56-3

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (2)
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

Pitolisant is a potent and selective nonimidazole inverse agonist at the recombinant human histamine H3 receptor (K_i=0.16 nM).

IC₅₀ & Target

Ki: 0.16 nM (H3 receptor)^[1]
EC50: 1.5 nM (H3 receptor)^[1]

All Histamine Receptor Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	IC₅₀	1.7 μM Compound: Pitolisant	Inhibition of human ERG expressed in CHO cells at holding potential of -90 mV by patch clamp method Inhibition of human ERG expressed in CHO cells at holding potential of -90 mV by patch clamp method	[PMID: 28797771]
CHO-K1	EC₅₀	1.5 nM Compound: BF2.649	Antagonist activity at human histamine H3 receptor expressed in CHO-K1 cells by [35S]GTPgammaS binding assay Antagonist activity at human histamine H3 receptor expressed in CHO-K1 cells by [35S]GTPgammaS binding assay	[PMID: 19329325]
CHO-K1	IC₅₀	12 nM Compound: 25, BF2.649	Antagonist activity at human cloned histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition of R-alpha-methylhistamine-induced [35S]GTPgammaS binding Antagonist activity at human cloned histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition of R-alpha-methylhistamine-induced [35S]GTPgammaS binding	[PMID: 18841880]

In Vitro

On the stimulation of guanosine 5′-O-(3-[³⁵S]thio)triphosphate binding to this receptor, Pitolisant (BF2.649) behaves as a competitive antagonist with a K_i value of 0.16 nM and as an inverse agonist with an EC₅₀ value of 1.5 nM and an intrinsic activity ~50% higher than that of ciproxifan. Pitolisant displaces [¹²⁵I]iodoproxyfan binding from mouse brain cortical membranes with an IC₅₀ value of 26.4±4.5 nM. Taking into account the K_d value of the radioligand (161±9 pM), the deduced K_i value for Pitolisant is 14±1 nM. Pitolisant displaces [¹²⁵I]iodoproxyfan binding from membranes of rat glioma C6 cells stably expressing the human H₃ receptor with an IC₅₀ value of 4.2±0.2 nM. Taking into account the K_d value of the radioligand (50±4 pM), the deduced K_i value for Pitolisant is 2.7±0.5 nM. Pitolisant progressively reverses this response with a Hill coefficient close to unity and an IC₅₀ value of 330±68 nM, leading to a K_i value of 17±4 nM. Pitolisant elicits a dose-dependent decrease of the basal-specific [³⁵S]GTPγS binding to membranes with a maximal effect corresponding to 75±1% of the basal-specific binding and an EC₅₀ value of 1.5±0.1 nM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

The administration of Pitolisantat a single dose of 10 mg/kg 30 min before a single dose of Olanzapine (2 mg/kg b.w.) also significantly affects immobility time in the FST. Subsequent administration of the aforementioned drug sequence in mice statistically significantly increases the duration of immobility in comparison to the time determined in the control group in the FST. It decreased locomotor activity as well. In contrast, the results obtained in subchronic treatment after fifteen administrations of both drugs (Pitolisant 10 mg/kg b.w., and after 30 min Olanzapine 2 mg/kg b.w., and again after 4 h Olanzapine 2 mg/kg b.w.) show that the administration of Pitolisant followed by that of Olanzapine equalized the locomotor activity in mice; in comparison to the level of motility in the control group, to which only Pitolisant is administered. More importantly, this combination of drugs significantly reduces immobility time to the level obtained in the control group in the forced swim test in mice [one-way ANOVA; F_(3,20)=4.226,P=0.0181]^[2]. Rats given Pitolisant (10 mg/kg) during the conditioning phase stayed 502±94 s on the paired texture, a value not statistically different from that of controls, indicating that Pitolisant did not support place preference^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 362665-56-3
Appearance Liquid (Density: 1.056 g/cm³)
Molecular Weight 295.85
Formula C₁₇H₂₆ClNO
Color Colorless to light yellow
SMILES

ClC1=CC=C(CCCOCCCN2CCCCC2)C=C1
Synonyms

Tiprolisant
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Pure form	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (2)

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Journal Impact Factor

CNS Neurosci Ther

Pitolisant Inhibits Alcohol Drinking and Improves Withdrawal Negative Affect Through Lateral Habenula Histaminergic Signaling in Mice. [Abstract]

2026 Jan;32(1):e70732. PMID: 41492821
Brain Res

In vivo evaluation of effects of histamine H3 receptor antagonists on methamphetamine-induced hyperlocomotion in mice. [Abstract]

2020 Aug 1;1740:146873. PMID: 32387137

Solvent & Solubility

In Vitro:

DMSO : 200 mg/mL (676.02 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

3.3801 mL

16.9005 mL

33.8009 mL

5 mM

0.6760 mL

3.3801 mL

6.7602 mL

10 mM

0.3380 mL

1.6900 mL

3.3801 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

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Molecular Weight Molecular Weight

Dilution Calculator

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (8.45 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (8.45 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (8.45 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protocol

Kinase Assay^[1]

[³⁵S]GTPγS binding assays are performed. CHO-K1 cells stably expressing the human H₃ receptor (~400 fmol/mg protein) are homogenized in ice-cold buffer (50 mM Tris/HCl, pH 7.4). Homogenates are centrifuged twice (20,000g for 10 min at 4°C), and the final pellet is resuspended in 50 volumes of buffer. Membranes (550 μg of protein) are pretreated with adenosine deaminase (1 U/mL) and incubated for 60 min at 25°C with 0.1 nM [³⁵S]GTPγS and the drugs to be tested in a final volume of 1 mL of assay buffer (50 mM Tris/HCl, 50 mM NaCl, 5 mM MgCl₂, 10 μM GDP, and 0.02% bovine serum albumin, pH 7.4). The nonspecific binding is determined using 10 μM nonradioactive GTPγS. Incubations are stopped by rapid filtration under vacuum through GF/B glass fiber filters. After washing with ice-cold water, the radioactivity trapped on filters is counted by liquid scintillation spectrometry. A similar assay is used to assess competitive antagonism. In brief, membranes (10 μg of protein) of HEK-293 cells stably expressing the human H₃ receptor (~600 fmol/mg protein) are preincubated in presence of Pitolisant in the buffer (50 mM Tris/HCl, pH 7.4, 10 mM MgCl₂, 100 mM NaCl, and 10 μM GDP) in a 96-well microplate under gentle agitation at room temperature (19-20°C) for 30 min before the addition of 0.1 nM [³⁵S]GTPγS (final volume 200 μL). The nonspecific binding is determined using a 10 μM concentration of nonradioactive GTPγS. After 30 min, incubations performed in triplicate are stopped by rapid filtration under vacuum on a Multiscreen MAFCOB50 microplate. Radioactivity trapped on filters is counted by liquid scintillation spectrometry^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[2]^[3]

Mice^[2]
Adult female Albino Swiss mice weighing 20-22 g are used in the study. Olanzapine or Pitolisant are suspended in 1 % Tween 80. The compounds or vehicle are administered intraperitoneally (i.p.) 30 min prior to the acute experiment. In the Pitolisant+Olanzapine group, Pitolisant is administered 15 min before Olanzapine. Subchronic treatment is done at about 9:00 am (0.2 mL Tween to control group, Pitolisant-10 mg/kg b.w. to Pitolisant group, Olanzapine-2 mg/kg b.w. to Olanzapine group, Pitolisant-10 mg/kg b.w. and Olanzapine after 15 min-2 mg/kg b.w. to Pitolisant+Olanzapine group) and at about 1:00 pm (Olanzapine group and Pitolisant+Olanzapine group).
Rats^[3]
Male Wistar rats (220-300 g) receive vehicle (methylcellulose 1%, p.o.), Pitolisant (10 mg/kg, p.o.) or D-amphetamine (2.5 mg/kg, i.p. in saline). Ninety minutes later, they are killed by decapitation and nucleus accumbens are dissected out, weighed, frozen in liquid nitrogen and stored at -80°C. Tissues are homogenized in 1 mL of a 0.4 N perchloric acid/2.7 mM EDTA solution. After centrifugation (8000 rpm, 20 min, 4°C), supernatants are analysed by HPLC coupled to electrochemical detection. Tissue concentrations of dopamine (DA), dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) are determined and the corresponding ratios (DOPAC/DA, HVA/DA) are calculated.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (278 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Ligneau X, et al. BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology. J Pharmacol Exp Ther. 2007 Jan;320(1):365-75. [Content Brief]

[2]. Dudek M, et al. H3 histamine receptor antagonist pitolisant reverses some subchronic disturbances induced by olanzapine in mice. Metab Brain Dis. 2016 Oct;31(5):1023-9. [Content Brief]

[3]. Uguen M, et al. Preclinical evaluation of the abuse potential of Pitolisant, a histamine H? receptor inverse agonist/antagonist compared with Modafinil. Br J Pharmacol. 2013 Jun;169(3):632-44. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	3.3801 mL	16.9005 mL	33.8009 mL	84.5023 mL
	5 mM	0.6760 mL	3.3801 mL	6.7602 mL	16.9005 mL
	10 mM	0.3380 mL	1.6900 mL	3.3801 mL	8.4502 mL
	15 mM	0.2253 mL	1.1267 mL	2.2534 mL	5.6335 mL
	20 mM	0.1690 mL	0.8450 mL	1.6900 mL	4.2251 mL
	25 mM	0.1352 mL	0.6760 mL	1.3520 mL	3.3801 mL
	30 mM	0.1127 mL	0.5633 mL	1.1267 mL	2.8167 mL
	40 mM	0.0845 mL	0.4225 mL	0.8450 mL	2.1126 mL
	50 mM	0.0676 mL	0.3380 mL	0.6760 mL	1.6900 mL
	60 mM	0.0563 mL	0.2817 mL	0.5633 mL	1.4084 mL
	80 mM	0.0423 mL	0.2113 mL	0.4225 mL	1.0563 mL
	100 mM	0.0338 mL	0.1690 mL	0.3380 mL	0.8450 mL

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Pitolisant

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Publications Citing Use of MedChemExpress (MCE) Pitolisant

All Histamine Receptor Isoforms

Biological Activity

Chemical Information

Publications (2)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Pitolisant Related Classifications

HY-12199 Related Classifications