Identification

Name
Pitolisant
Accession Number
DB11642
Description

Pitolisant is a selective antagonist or inverse agonist of the histamine H3 receptor used to treat type 1 or 2 narcolepsy.8,10 Narcolepsy is a chronic neurological disorder that affects 1 in 2,000 individuals and is characterized by excessive daytime sleepiness, abnormal REM sleep manifestations, sleep paralysis and hypnagogic hallucinations.4 About 60-70% of patients with narcolepsy experience cataplexy, which is a sudden loss of muscle tone triggered by positive or negative emotions.1 Histaminergic neuron signalling in the brain plays a role in maintaining wakefulness; by blocking histamine autoreceptors, pitolisant enhances the activity of histaminergic neurons, as well as increasing the signalling of other neurotransmitters in the brain.8

In a European clinical trial of adult patients with narcolepsy, there was a reduction in the Epworth Sleepiness Scale (ESS) score from pitolisant therapy compared to placebo.3 The therapeutic effectiveness of pitolisant was comparable to that of modafinil.3 Pitolisant therapy was also effective in treating refractory sleepiness in adolescent patients with narcolepsy, where it decreased ESS score and increased the mean sleep onset latency.2 Adolescent patients with cataplexy also experienced a slight improvement in the frequency and severity of symptoms 2; however, the safety of use in adolescent or paediatric patients have not been established with pitolisant. Commonly marketed under the trade name Wakix, oral pitolisant was approved by the EMA in 2016 7 for the treatment of narcolepsy with or without cataplexy.8 FDA approved the use of pitolisant in 2019 for excessive daytime sleepiness (EDS) associated with narcolepsy in adults.10

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 295.85
Monoisotopic: 295.1702922
Chemical Formula
C17H26ClNO
Synonyms
  • Pitolisant
External IDs
  • BF-2.649
  • BF-2649
  • BF2.649

Pharmacology

Indication

Pitolisant is indicated for the treatment of narcolepsy with or without cataplexy 8 and excessive daytime sleepiness in narcolepsy in adult patients.10

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Pitolisant promotes wakefulness in narcolepsy by enhancing histaminergic signalling in the central nervous system. It does not significantly bind to H1, H2, or H4 receptors.10 In patients with narcolepsy in presence or absence of cataplexy, treatment of pitolisant was associated with an improvement in the level and duration of wakefulness and daytime alertness assessed by objective measures of ability to sustain wakefulness (e.g. Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) Scores) and attention (e.g. Sustained Attention to Response Task (SART)).8 Pitolisant also improved the frequency and severity of narcolepsy-associated cataplexy.1 Pitolisant acts as a blocker at hERG channels. In two QT studies, supra-therapeutic doses of pitolisant (3-6-times the therapeutic dose, that is 108 mg to 216 mg) produced mild to moderate prolongation of QTc interval (10-13 ms).8

Mechanism of action

Signalling of histaminergic neurons plays a key role in activating the arousal system with widespread projections to the whole brain 8 via activating orexin receptors.1 Narcolepsy is characterized by insufficient neurotransmission by orexins, or hypocretins, which are excitatory peptides released by neurons located from the lateral hypothalamus. These neurons project to aminergic neurons, such as histaminergic or noradrenergic neurons, that are responsible for the effects of orexin and control of wakefulness.4 Histamine H3 receptors are presynaptic inhibitory autoreceptors 6 that are located in the cerebral cortex, hypothalamus, hippocampus, and basal ganglia.5 H3 receptors promote the re-uptake of histamine at synaptic terminals and attenuate further histamine release into the synapse.4 By blocking H3 autoreceptors and increasing the levels of histamine transmitters at the synapse, pitolisant enhances the activity of histaminergic neurons and promotes wakefulness.8 Inverse agonism of pitolisant at H3 receptors also leads to enhanced synthesis and release of endogenous histamine over the basal level.4

Pitolisant acts as a high-affinity competitive antagonist (Ki 0.16 nM) and as an inverse agonist (EC50 1.5 nM) at the human H3 receptor 1 and mediates its pharmacological action at the presynaptic level.5 It is thought to bind to the antagonist binding site of the H3 receptor, which is located within the transmembrane core just below the extracellular loops. Piperidines form a salt bridge with Glu206 in the membrane-spanning segment, and the hydroxyl of Tyr374 is H-bonded with the central oxygen of piperidine.4 Pitolisant displays high selectivity for H3 receptors compared to other histamine receptor subtypes. Pitolisant also modulates acetylcholine, noradrenaline and dopamine release in the brain by increasing the levels of neurotransmitters but does not increase dopamine release in the stratal complex, including the nucleus accumbens.8 At lower nanomolar concentrations, pitolisant acts as an inverse agonist at H3 receptors and enhances the release of endogenous histamine over the basal level.4

TargetActionsOrganism
AHistamine H3 receptor
antagonist
inverse agonist
Humans
NPotassium voltage-gated channel subfamily H member 2
blocker
Humans
Absorption

Pitolisant is rapidly and well absorbed following oral administration, resulting in the drug being 90% absorbed.10 In healthy individuals receiving an oral dose of 20 mg, the Cmax was approximately 30 ng/mL.4 Following oral administration of pitolisant 35.6 mg once daily, the mean steady state Cmax and AUC were 73 ng/mL and 812 ngxhr/mL, respectively.10 The Tmax was typically reached approximately 3 hours following administration.8 Following repeated dosing, the steady-state plasma concentration is achieved after 5-6 days of administration but the inter-individual variability in the time to reach steady-state is reported to be high.8 The absolute bioavailability of pitolisant has not been determined.9

Volume of distribution

Following single and multiple oral dosing of pitolisant to healthy male adults at doses between 1 and 240 mg, the apparent volume of distribution (V/F) ranges from 1100 to 2825 L.9 Pitolisant is thought to be equally distributed between red blood cells and plasma.8 Following intravenous administration of pitolisant in rats and monkeys, the apparent Vd at steady-state was approximately 10-fold greater than total body water.9 Pitolisant crosses the blood-brain barrier and placenta, and was found in milk in rats.9

Protein binding

The serum protein binding of pitolisant is approximately 91% to 96%.10 Pitolisant is mainly bound to serum albumin and alpha-1 glycoprotein.12

Metabolism

Pitolisant is primarily metabolized by CYP2D6 and to a lesser extent by CYP3A4 in the liver. The major non-conjugated metabolites are BP2.941 (piperidine N-oxide) and BP2.951 (5-aminovaleric acid).8 Metabolites can further undergo conjugation with glycine or glucuronic acid, and oxidation to a minimal extent.9 Most metabolites of pitolisant do not retain considerable pharmacological activities.10 Several conjugated metabolites were also identified; the major conjugated inactive metabolite was a glycine conjugate of the acid metabolite of O-dealkylated desaturated pitolisant and a glucuronide of a ketone metabolite of monohydroxy desaturated pitolisant.8

Due to its extensive metabolism in the liver, the systemic exposure of pitolisant thus adverse events of the drug may be elevated in case of compromised liver function. The dosage adjustments for pitolisant is advised in patients with moderate hepatic impairment.10

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Route of elimination

Following hepatic metabolism, about 63% of total elimination occurs via renal excretion into the urine as an inactive non-conjugated metabolite BP2.951 and a glycine conjugated metabolite.8 About 25% of the total dose administered is excreted through expired air as metabolites, and a small fraction (<3%) of drug can be recovered in faeces.8

Half-life

Pitolisant has a plasma half-life of 10-12 hours.8 After administration of a single dose of 35.6 mg, the median half-life of pitolisant was approximately 20 hours.10

Clearance

The apparent oral clearance (CL/F) of pitolisant was 43.9 L/hr following a single dose of 35.6 mg.10 The clearance rate is expected to be lower with increasing age.9

Adverse Effects
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Toxicity

Symptoms of pitolisant overdose may include headache, insomnia, irritability, nausea and abdominal pain. In case of overdose, hospitalisation and monitoring of the vital functions are recommended. There is no clearly identified antidote.8

After 1 month in mice, 6 months in rats and 9 months in monkeys, no adverse effect level (NOAEL) were 75, 30 and 12 mg/kg/day, p.o., respectively.8 Pitolisant was not found to be genotoxic in Ames test nor carcinogenic in mouse and rat carcinogenicity studies.9 In rabbit and rat teratogenicity studies, maternally high toxic doses of pitolisant sperm morphology abnormalities and decreased motility without any significant effect on fertility indexes in male rats. It also decreased the percentage of live conceptuses and increased post-implantation loss in female rats. A delay in post-natal development was observed.8

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Pitolisant which could result in a higher serum level.
AbametapirThe serum concentration of Pitolisant can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Pitolisant can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Pitolisant.
AbirateroneThe serum concentration of Abiraterone can be decreased when it is combined with Pitolisant.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Pitolisant.
AcarboseAcarbose may decrease the excretion rate of Pitolisant which could result in a higher serum level.
AcebutololAcebutolol may increase the QTc-prolonging activities of Pitolisant.
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Pitolisant.
AcemetacinThe risk or severity of adverse effects can be increased when Acemetacin is combined with Pitolisant.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

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Food Interactions
  • Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of pitolisant. Dose adjustment may be necessary for co-administration.
  • Take with or without food. A high-fat meal had no clinically significant effects on drug pharmacokinetics.

Products

Product Ingredients
IngredientUNIICASInChI Key
Pitolisant hydrochlorideYV33CH63HI903576-44-3XLFKECRRMPOAQS-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
WakixTablet, film coated4.45 mg/1OralHarmony Biosciences, Llc2019-08-14Not applicableUS flag
WakixTablet, film coated18 mgOralBioprojet Pharma2016-03-31Not applicableEU flag
WakixTablet, film coated17.8 mg/1OralHarmony Biosciences, Llc2019-08-14Not applicableUS flag
WakixTablet, film coated4.5 mgOralBioprojet Pharma2016-03-31Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
N07XX11 — Pitolisant
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as chlorobenzenes. These are compounds containing one or more chlorine atoms attached to a benzene moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Chlorobenzenes
Alternative Parents
Piperidines / Aryl chlorides / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Amine / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Chlorobenzene / Dialkyl ether / Ether / Hydrocarbon derivative / Organic nitrogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
4BC83L4PIY
CAS number
362665-56-3
InChI Key
NNACHAUCXXVJSP-UHFFFAOYSA-N
InChI
InChI=1S/C17H26ClNO/c18-17-9-7-16(8-10-17)6-4-14-20-15-5-13-19-11-2-1-3-12-19/h7-10H,1-6,11-15H2
IUPAC Name
1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine
SMILES
ClC1=CC=C(CCCOCCCN2CCCCC2)C=C1

References

General References
  1. Calik MW: Update on the treatment of narcolepsy: clinical efficacy of pitolisant. Nat Sci Sleep. 2017 Apr 26;9:127-133. doi: 10.2147/NSS.S103462. eCollection 2017. [PubMed:28490912]
  2. Inocente C, Arnulf I, Bastuji H, Thibault-Stoll A, Raoux A, Reimao R, Lin JS, Franco P: Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness. Clin Neuropharmacol. 2012 Mar-Apr;35(2):55-60. doi: 10.1097/WNF.0b013e318246879d. [PubMed:22356925]
  3. Dauvilliers Y, Bassetti C, Lammers GJ, Arnulf I, Mayer G, Rodenbeck A, Lehert P, Ding CL, Lecomte JM, Schwartz JC: Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol. 2013 Nov;12(11):1068-75. doi: 10.1016/S1474-4422(13)70225-4. Epub 2013 Oct 7. [PubMed:24107292]
  4. Schwartz JC: The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br J Pharmacol. 2011 Jun;163(4):713-21. doi: 10.1111/j.1476-5381.2011.01286.x. [PubMed:21615387]
  5. Romigi A, Vitrani G, Lo Giudice T, Centonze D, Franco V: Profile of pitolisant in the management of narcolepsy: design, development, and place in therapy. Drug Des Devel Ther. 2018 Aug 30;12:2665-2675. doi: 10.2147/DDDT.S101145. eCollection 2018. [PubMed:30214155]
  6. Kotanska M, Kuder KJ, Szczepanska K, Sapa J, Kiec-Kononowicz K: The histamine H3 receptor inverse agonist pitolisant reduces body weight in obese mice. Naunyn Schmiedebergs Arch Pharmacol. 2018 Aug;391(8):875-881. doi: 10.1007/s00210-018-1516-2. Epub 2018 May 25. [PubMed:29802412]
  7. Ligneau X, Shah RR, Berrebi-Bertrand I, Mirams GR, Robert P, Landais L, Maison-Blanche P, Faivre JF, Lecomte JM, Schwartz JC: Nonclinical cardiovascular safety of pitolisant: comparing International Conference on Harmonization S7B and Comprehensive in vitro Pro-arrhythmia Assay initiative studies. Br J Pharmacol. 2017 Dec;174(23):4449-4463. doi: 10.1111/bph.14047. Epub 2017 Oct 19. [PubMed:28941245]
  8. Wakix, INN-Pitolisant - European Medicines Agency - Europa EU [Link]
  9. Wakix, INN-pitolisant - European Medicines Agency - Europa EU: Assessment report [Link]
  10. WAKIX® (pitolisant) tablets, for oral use - FDA Label [Link]
  11. Harmony Biosciences: Wakix (pitolisant) Safety data sheet [Link]
  12. FDA Center for Drug Evaluation and Research: Pitolisant Non-clinical Review(s) [Link]
ChemSpider
8123714
BindingDB
50247053
RxNav
2197878
ChEBI
134709
ChEMBL
CHEMBL462605
ZINC
ZINC000034045468
Wikipedia
Pitolisant

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentCataplexy / Excessive Daytime Sleepiness / Narcolepsy1
3CompletedTreatmentCataplexy / Excessive Daytime Sleepiness / Narcolepsy / Sleep disorders and disturbances1
3CompletedTreatmentCataplexy / Narcolepsy1
3CompletedTreatmentExcessive Daytime Sleepiness / Narcolepsy With Cataplexy1
3CompletedTreatmentExcessive Daytime Sleepiness / Obstructive Sleep Apnea (OSA)3
3CompletedTreatmentNarcolepsy1
3CompletedTreatmentParkinson's Disease (PD)2
3CompletedTreatmentTreatment of Excessive Daytime Sleepiness in Narcolepsy1
3WithdrawnTreatmentExcessive Daytime Sleepiness / Obstructive Sleep Apnea (OSA)1
2Active Not RecruitingTreatmentNarcolepsy With Cataplexy / Narcolepsy Without Cataplexy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral17.8 mg/1
Tablet, film coatedOral18 mg
Tablet, film coatedOral4.45 mg/1
Tablet, film coatedOral4.5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8354430No2013-01-152026-02-26US flag
US7910605No2011-03-222022-09-23US flag
US8486947No2013-07-162029-09-26US flag
US7169928No2007-01-302020-02-02US flag
US8207197No2012-06-262029-02-25US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00142 mg/mLALOGPS
logP4.47ALOGPS
logP4.12ChemAxon
logS-5.3ALOGPS
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity86.81 m3·mol-1ChemAxon
Polarizability35.5 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Inverse agonist
Curator comments
Pitolisant acts as a high-affinity competitive antagonist (Ki 0.16 nM) and as an inverse agonist (EC50 1.5 nM) at the human histamine H3 receptor subtype.
General Function
Histamine receptor activity
Specific Function
The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive a...
Gene Name
HRH3
Uniprot ID
Q9Y5N1
Uniprot Name
Histamine H3 receptor
Molecular Weight
48670.81 Da
References
  1. Schwartz JC: The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br J Pharmacol. 2011 Jun;163(4):713-21. doi: 10.1111/j.1476-5381.2011.01286.x. [PubMed:21615387]
  2. Khanfar MA, Affini A, Lutsenko K, Nikolic K, Butini S, Stark H: Multiple Targeting Approaches on Histamine H3 Receptor Antagonists. Front Neurosci. 2016 May 30;10:201. doi: 10.3389/fnins.2016.00201. eCollection 2016. [PubMed:27303254]
  3. Inocente C, Arnulf I, Bastuji H, Thibault-Stoll A, Raoux A, Reimao R, Lin JS, Franco P: Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness. Clin Neuropharmacol. 2012 Mar-Apr;35(2):55-60. doi: 10.1097/WNF.0b013e318246879d. [PubMed:22356925]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Blocker
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Ligneau X, Shah RR, Berrebi-Bertrand I, Mirams GR, Robert P, Landais L, Maison-Blanche P, Faivre JF, Lecomte JM, Schwartz JC: Nonclinical cardiovascular safety of pitolisant: comparing International Conference on Harmonization S7B and Comprehensive in vitro Pro-arrhythmia Assay initiative studies. Br J Pharmacol. 2017 Dec;174(23):4449-4463. doi: 10.1111/bph.14047. Epub 2017 Oct 19. [PubMed:28941245]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Pitolisant is an inhibitor of CYP2D6 with moderate potency (IC50 = 2.6 μM).
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
Curator comments
Inhibition of CYP1A2 by pitolisant was observed in vitro.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Pitilosant FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
Curator comments
Inhibition of CYP2B6 by pitolisant was observed in vitro.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Pitolisant EMA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
Curator comments
Induction of CYP3A4 by pitolisant was observed in vitro.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Center for Drug Evaluation and Research: Pitolisant Non-clinical Review(s) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. FDA Center for Drug Evaluation and Research: Pitolisant Non-clinical Review(s) [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Pitolisant shows greater than 50% inhibition towards OCT1 (organic cation transporters 1) at 1.33 μM, and the extrapolated IC50 of pitolisant is 0.795 μM.
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Romigi A, Vitrani G, Lo Giudice T, Centonze D, Franco V: Profile of pitolisant in the management of narcolepsy: design, development, and place in therapy. Drug Des Devel Ther. 2018 Aug 30;12:2665-2675. doi: 10.2147/DDDT.S101145. eCollection 2018. [PubMed:30214155]
  2. Wakix EPAR (EMA) [File]

Drug created on October 17, 2016 15:30 / Updated on June 12, 2020 10:53

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