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Details

Stereochemistry ACHIRAL
Molecular Formula C17H26ClNO
Molecular Weight 295.847
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PITOLISANT

SMILES

ClC1=CC=C(CCCOCCCN2CCCCC2)C=C1

InChI

InChIKey=NNACHAUCXXVJSP-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description

Pitolisant (INN) or tiprolisant (USAN) is a histamine receptor inverse agonist/antagonist selective for the H3 subtype. It has stimulant and nootropic effects in animal studies and may have several medical applications, having been researched for the treatment of narcolepsy, for which it has been granted orphan drug status in the EU and US. It is currently in clinical trials for schizophrenia and Parkinson’s disease. Pitolisant hydrochloride was approved by European Medicine Agency (EMA) on Mar 31, 2016. It was developed and marketed as Wakix® by Bioprojet in EU. Wakix® is available as the tablet for oral use, containing 4.5 mg and 18 mg of Pitolisant hydrochloride. The initial dose of 9 mg (two 4.5 mg, tablets) per day, and it should be used at the lowest effective dose, depending on individual patient response and tolerance, according to an up-titration scheme, without exceeding the dose of 36 mg/day. Pitolisant was the first clinically used H3 receptor inverse agonist.

CNS Activity

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1148.15 nM [Ki]
12.0 nM [IC50]
Conditions
PubMed

PubMed

TitleDatePubMed
Keynote review: histamine H3 receptor antagonists reach out for the clinic.
2005 Dec
Brain histamine and schizophrenia: potential therapeutic applications of H3-receptor inverse agonists studied with BF2.649.
2007 Apr 15
BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.
2007 Jan
Histamine H3 antagonists as wake-promoting and pro-cognitive agents.
2008
An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients.
2008 Apr
Diether derivatives of homo- or substituted piperidines as non-imidazole histamine H3 receptor ligands.
2009 Apr 15
5-hydroxyindole-2-carboxylic acid amides: novel histamine-3 receptor inverse agonists for the treatment of obesity.
2009 Jul 9
Recent advances in histamine H3 receptor antagonists/inverse agonists.
2010 Sep
Discovery and characterization of 6-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2H-pyridazin-3-one (CEP-26401, irdabisant): a potent, selective histamine H3 receptor inverse agonist.
2011 Jul 14
The histamine H3 receptor: from discovery to clinical trials with pitolisant.
2011 Jun
International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.
2015 Jul
Patents

Sample Use Guides

In Vivo Use Guide
Wakix (Pitolisant) should be used at the lowest effective dose, depending on individual patient response and tolerance, according to an up-titration scheme, without exceeding the dose of 36 mg/day: - Week 1: initial dose of 9 mg (two 4.5 mg tablets) per day. - Week 2: the dose may be increased to 18 mg (one 18 mg tablet) per day or decreased to 4.5 mg (one 4.5 mg tablet) per day. - Week 3: the dose may be increased to 36 mg (two 18 mg tablets) per day. At any time the dose can be decreased (down to 4.5 mg per day) or increased (up to 36 mg per day) according to the physician assessment and the patient’s response.
Route of Administration: Oral
In Vitro Use Guide
Longitudinal muscle strips from small intestine from guinea pig were dissected out and incubated in a gassed O2/CO2 (95%/5%) modified Krebs-Ringer bicarbonate medium at 37°C in presence of 1 mkM mepyramine to block H1 receptors. After equilibration, contractile activity under stimulation (rectangular pulses of 15 V, 0.5 ms, and 0.1 Hz) was recorded. Concentration-response curves of the effect of (R)-alpha-MeHA alone or together with BF2.649 (Pitolisant) were performed.
Name Type Language
PITOLISANT
WHO-DD  
INN   USAN  
Official Name English
BF2.649
Code English
HBS-101
Code English
PITOLISANT [USAN]
Common Name English
PITOLISANT [WHO-DD]
Common Name English
3-(4-CHLOROPHENYL)PROPYL 3-PIPERIDINOPROPYL ETHER
Systematic Name English
1-(3-(3-(4-CHLOROPHENYL)PROPOXY)PROPYL)PIPERIDINE
Systematic Name English
PITOLISANT [INN]
Common Name English
BF-2.649
Code English
PIPERIDINE, 1-(3-(3-(4-CHLOROPHENYL)PROPOXY)PROPYL)-
Systematic Name English
BF-2649
Code English
Classification Tree Code System Code
WHO-ATC N07XX11
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
FDA ORPHAN DRUG 307210
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL462605
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
PRIMARY
EVMPD
SUB174467
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
PRIMARY
INN
8952
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
PRIMARY
EVMPD
SUB166257
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
PRIMARY
PUBCHEM
9948102
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
PRIMARY
WIKIPEDIA
PITOLISANT
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
PRIMARY
MESH
C516975
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
PRIMARY
CAS
362665-56-3
Created by admin on Mon Oct 21 19:43:50 UTC 2019 , Edited by admin on Mon Oct 21 19:43:50 UTC 2019
PRIMARY