Pitolisant hydrochlorideProduct ingredient for Pitolisant

Name
Pitolisant hydrochloride
Drug Entry
Pitolisant

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

Accession Number
DBSALT002888
Structure
Thumb
Synonyms
Ciproxidine / Pitolisant HCl / Tiprolisant
UNII
YV33CH63HI
CAS Number
903576-44-3
Weight
Average: 332.31
Monoisotopic: 331.1469699
Chemical Formula
C17H27Cl2NO
InChI Key
XLFKECRRMPOAQS-UHFFFAOYSA-N
InChI
InChI=1S/C17H26ClNO.ClH/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;1H
IUPAC Name
1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine hydrochloride
SMILES
Cl.ClC1=CC=C(CCCOCCCN2CCCCC2)C=C1
ChemSpider
9726467
Wikipedia
Pitolisant
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