PITOLISANT

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 Search

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

Molecular Formula	C17H26ClNO
Molecular Weight	295.847
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002616/WC500204746.pdf
Curator's Comment: description was created based on several sources, including https://www.google.com/patents/WO2000006254A2 | https://www.drugs.com/uk/wakix.html | https://www.ncbi.nlm.nih.gov/pubmed/28087755 | https://www.ncbi.nlm.nih.gov/pubmed/27568835 | https://www.ncbi.nlm.nih.gov/pubmed/27223666

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H3 receptor 46 Target ID: CHEMBL264 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18841880	Inverse Agonist 85		12.0 nM [IC50]
Histamine H1 receptor 316 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24650714	Antagonist 2849		1148.15 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Narcolepsy without cataplexy 3 Sources: https://clinicaltrials.gov/ct2/show/NCT01800045	Primary	Approved 8583	Wakix Approved Use Therapeutic indications. Wakix is indicated in adults for the treatment of narcolepsy with or without cataplexy
Narcolepsy without cataplexy 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02611687	Primary	Approved 8583	Wakix Approved Use Therapeutic indications. Wakix is indicated in adults for the treatment of narcolepsy with or without cataplexy
Parkinson's disease 232 Sources: https://clinicaltrials.gov/ct2/show/NCT01066442	Primary	Phase III 665	Wakix Approved Use Therapeutic indications. Wakix is indicated in adults for the treatment of narcolepsy with or without cataplexy

C_max

Value	Dose	Co-administered	Analyte	Population
73 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211150s000lbl.pdf	35.6 mg 1 times / day steady-state, oral dose: 35.6 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PITOLISANT serum	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
812 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211150s000lbl.pdf	35.6 mg 1 times / day steady-state, oral dose: 35.6 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PITOLISANT serum	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211150s000lbl.pdf	35.6 mg 1 times / day steady-state, oral dose: 35.6 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PITOLISANT serum	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
6.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211150s000lbl.pdf	35.6 mg 1 times / day steady-state, oral dose: 35.6 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PITOLISANT serum	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
240 mg single, oral Highest studied dose Dose: 240 mg Route: oral Route: single Dose: 240 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf	healthy, adults Health Status: healthy Age Group: adults Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf
50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf	healthy, adults Health Status: healthy Age Group: adults Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf
53.4 mg 1 times / day steady, oral Highest studied dose Dose: 53.4 mg, 1 times / day Route: oral Route: steady Dose: 53.4 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf	unhealthy, adults Health Status: unhealthy Age Group: adults Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf
17.8 mg 1 times / day multiple, oral Recommended Dose: 17.8 mg, 1 times / day Route: oral Route: multiple Dose: 17.8 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf	unhealthy, adults Health Status: unhealthy Age Group: adults Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf	Disc. AE: Anxiety, Depression... Other AEs: Anxiety, Depression... AEs leading to discontinuation/dose reduction: Anxiety Depression Insomnia Hypnagogic hallucination Cataplexy Myalgia Somnolence Abdominal pain Headache Other AEs: Anxiety Depression Insomnia Hypnagogic hallucination Cataplexy Myalgia Somnolence Abdominal pain Headache Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf
35.6 mg 1 times / day multiple, oral Recommended Dose: 35.6 mg, 1 times / day Route: oral Route: multiple Dose: 35.6 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211150s000lbl.pdf	unhealthy, adults Health Status: unhealthy Age Group: adults Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211150s000lbl.pdf	Other AEs: Cluster headache, Headache... Other AEs: Cluster headache (18%) Headache (18%) Migraine (18%) Premenstrual headache (18%) Tension headache (18%) Initial insomnia (6%) Insomnia (6%) Middle insomnia (6%) Poor quality sleep (6%) Nausea (6%) Pharyngitis (5%) Rhinitis (5%) Sinusitis (5%) Upper respiratory tract infection (5%) Upper respiratory tract inflammation (5%) Viral upper respiratory tract infection (5%) Arthralgia (5%) Back pain (5%) Carpal tunnel syndrome (5%) Limb discomfort (5%) Musculoskeletal pain (5%) Myalgia (5%) Neck pain (5%) Osteoarthritis (5%) Pain in extremity (5%) Sciatica (5%) Nervousness (5%) Stress (5%) Stress at work (5%) Heart rate increased (3%) Sinus tachycardia (3%) Tachycardia (3%) Hallucination visual (3%) Hypnagogic hallucination (3%) Irritability (3%) Abdominal discomfort (3%) Abdominal pain (3%) Abdominal pain upper (3%) Dyssomnia (3%) Sleep disorder (3%) Sleep paralysis (3%) Sleep talking (3%) Decreased appetite (3%) Cataplexy (2%) Dry mouth (2%) Eczema (2%) Erythema migrans (2%) Rash (2%) Urticaria (2%) Cluster headache (18%) Headache (18%) Migraine (18%) Premenstrual headache (18%) Tension headache (18%) Initial insomnia (6%) Insomnia (6%) Middle insomnia (6%) Poor quality sleep (6%) Nausea (6%) Pharyngitis (5%) Rhinitis (5%) Sinusitis (5%) Upper respiratory tract infection (5%) Upper respiratory tract inflammation (5%) Viral upper respiratory tract infection (5%) Arthralgia (5%) Back pain (5%) Carpal tunnel syndrome (5%) Limb discomfort (5%) Musculoskeletal pain (5%) Myalgia (5%) Neck pain (5%) Osteoarthritis (5%) Pain in extremity (5%) Sciatica (5%) Nervousness (5%) Stress (5%) Stress at work (5%) Heart rate increased (3%) Sinus tachycardia (3%) Tachycardia (3%) Hallucination visual (3%) Hypnagogic hallucination (3%) Irritability (3%) Abdominal discomfort (3%) Abdominal pain (3%) Abdominal pain upper (3%) Dyssomnia (3%) Sleep disorder (3%) Sleep paralysis (3%) Sleep talking (3%) Decreased appetite (3%) Cataplexy (2%) Dry mouth (2%) Eczema (2%) Erythema migrans (2%) Rash (2%) Urticaria (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211150s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252 substrate 1946	inducer 440 inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 BCRP 910 OATP1B1 1079 OATP1B3 961 OAT1 725 OAT3 747 OCT2 779 MATE1 415 MATE2 267 OCT1 620 CYP1A2 2153 CYP2A6 879 CYP2C19 2057 CYP2E1 1060	P-gp 2052 BCRP 697 OATP1B1 503 OATP1B3 435 OCT1 393	CYP1A2 832 CYP2A6 86 CYP2C19 329 CYP2E1 131 UGT1A1 78 UGT1A4 5 UGT1A6 34 UGT1A9 9 UGT2B7 14 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
CYP2A6 911	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
CYP2E1 1146	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT1A1 303	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT1A4 100	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT1A6 171	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT1A9 155	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT2B7 210	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf#page=29 Page: 29,79	weak	no (co-administration study) Comment: pitolisant does not affect the PK of bupropion (150 mg single dose) and, therefore, does not induce CYP2B6 metabolism. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf#page=29 Page: 29,79
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf#page=78 Page: 38.0	weak	weak (co-administration study) Comment: using mRNA analysis; weak induction by pitolisant and BP2.951 at 50-fold Cmax at MRHD; pitolisant reduces exposures of midazolam (2.5 mg single dose) about 20%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf#page=78 Page: 38.0
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	yes [IC50 0.795 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	yes [IC50 2.6 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf#page=61 Page: 61.0	yes	yes (co-administration study) Comment: paroxetine (as inhibitor) increased the Cmax and AUC of pitolisant by 1.5-fold and 2.2-fold, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf#page=61 Page: 61.0
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf#page=70 Page: 70.0	yes	yes (co-administration study) Comment: rifampicin (as inducer) decreased pitolisant Cmax and AUC and by 39% and 48%, respectively; pitosilant with itraconazole had negligible effect on the PK of pitolisant Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf#page=70 Page: 70.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000ClinPharmR.pdf#page=23 Page: 23.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY428143	https://www.001chemical.com/chem/362665-56-3
001 Chemical	DY428144	https://www.001chemical.com/chem/903576-44-3
AA Blocks	AA003TQC	https://www.aablocks.com/goods/Goods/detail?id=AA003TQC
Aaron Chemicals	AR003UI4	http://www.aaronchem.com/362665-56-3
abcr GmbH	AB494593	http://www.abcr.com/shop/en/AB494593
Acadechem	ACDS-056562	http://www.acadechemical.com/product/131261
Achemtek	0102-012214	http://www.achemtek.com/362665-56-3
AK Scientific, Inc. (AKSCI)	3973AH	http://www.aksci.com/item_detail.php?cat=3973AH
Ambeed	A556956	https://www.ambeed.com/products/362665-56-3.html
Ambinter	Amb23594586	http://www.ambinter.com/reference/23594586
Angene	AGN-PC-0MW5N5	http://www.angenechemical.com/productshow/AGN-PC-0MW5N5.html
Aurora Fine Chemicals LLC	A24.138.843	http://online.aurorafinechemicals.com/info?ID=A24.138.843
Aurum Pharmatech LLC	W-5790	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5790
BioChemPartner	BCP13114	http://www.biochempartner.com/362665-56-3-BCP13114
BioCrick	BCC1862	http://www.biocrick.com/Pitolisant-BCC1862.html
BLD Pharm	BD628804	http://www.bldpharm.com/products/362665-56-3.html
Chem Scene	CS-0666	http://www.chemscene.com/362665-56-3.html
Chemspace	CSSB00015189876	https://chem-space.com/CSSB00015189876
CSNpharm	CSN17352	https://www.csnpharm.com/products/pitolisant.html
DC Chemicals	DC22377	http://www.dcchemicals.com/product_show-DC22377.html
Debye Scientific	DB-115766	http://www.debyesci.com/cas_362665-56-3.html
Excenen	EX-A3601	https://www.excenen.com/searchresultlist.php?id=EX-A3601
Lab Network	LN00334401	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00334401
Matrix Scientific	146147	https://www.matrixscientific.com/146147.html
MedChem Express	HY-12199	https://www.medchemexpress.com/pitolisant.html
Molcore	MC428143	https://www.molcore.com/product/362665-56-3
Molcore	MC428144	https://www.molcore.com/product/903576-44-3
MuseChem	I003332	https://www.musechem.com/product/I003332.html
Sinfoo Biotech	S040905	http://www.sinfoobiotech.com/product/1044303
Smolecule	S635256	https://www.smolecule.com/products/s635256
Synblock Inc	SB17037	http://www.synblock.com/product/362665-56-3.html
THE BioTek	bt-340186	https://www.thebiotek.com/product/others/bt-340186

PubMed

Title	Date	PubMed
International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.	2015-07	26084539
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.	2011-07-14	21634396
The histamine H3 receptor: from discovery to clinical trials with pitolisant.	2011-06	21615387
Recent advances in histamine H3 receptor antagonists/inverse agonists.	2010-09	20716022
5-hydroxyindole-2-carboxylic acid amides: novel histamine-3 receptor inverse agonists for the treatment of obesity.	2009-07-09	19456097
Diether derivatives of homo- or substituted piperidines as non-imidazole histamine H3 receptor ligands.	2009-04-15	19329325
An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients.	2008-04	18295497
Histamine H3 antagonists as wake-promoting and pro-cognitive agents.	2008	18673168
Brain histamine and schizophrenia: potential therapeutic applications of H3-receptor inverse agonists studied with BF2.649.	2007-04-15	17343831
BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.	2007-01	17005916
Keynote review: histamine H3 receptor antagonists reach out for the clinic.	2005-12	16376822

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:54:26 GMT 2025` Edited by `admin` on `Mon Mar 31 20:54:26 GMT 2025`
Record UNII	4BC83L4PIY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PITOLISANT

Official Name

English

pitolisant [INN]

Preferred Name

English

BF2.649

Code

English

HBS-101

Code

English

PITOLISANT [USAN]

Common Name

English

PITOLISANT [MI]

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 [WHO-DD]

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

FDA ORPHAN DRUG

307210