PITOLISANT HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H26ClNO.ClH
Molecular Weight	332.308
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.ClC1=CC=C(CCCOCCCN2CCCCC2)C=C1

InChI

InChIKey=XLFKECRRMPOAQS-UHFFFAOYSA-N

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

HIDE SMILES / InChI

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 44 Target ID: CHEMBL264 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18841880	Inverse Agonist 80		12.0 nM [IC50]
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24650714	Antagonist 2778		1148.15 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Narcolepsy without cataplexy 3 Sources: https://clinicaltrials.gov/ct2/show/NCT01800045	Primary	Approved 8429	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 8429	Wakix Approved Use Therapeutic indications. Wakix is indicated in adults for the treatment of narcolepsy with or without cataplexy
Parkinson's disease 226 Sources: https://clinicaltrials.gov/ct2/show/NCT01066442	Primary	Phase III 656	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 unknown	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 unknown	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 unknown	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 unknown	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 (max) 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 n = 6 Health Status: unhealthy Condition: excessive daytime sleepiness (EDS) Age Group: adults Sex: unknown Population Size: 6 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 (max) 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 Page: P09-15	unhealthy, adults n = 166 Health Status: unhealthy Condition: excessive daytime sleepiness (EDS) Age Group: adults Sex: unknown Population Size: 166 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000SumR.pdf Page: P09-15	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 Page: P09-15
35.6 mg 1 times / day multiple, oral (typical) 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 n = 152 Health Status: unhealthy Condition: excessive daytime sleepiness (EDS) Age Group: adults Sex: unknown Population Size: 152 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 781 inhibitor 1587 substrate 1737	inducer 389 inhibitor 1767	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT2 647 MATE1 306 MATE2 263 OCT1 512 CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882	P-gp 1537 BCRP 561 OATP1B1 406 OATP1B3 350 OCT1 327	CYP1A2 701 CYP2A6 79 CYP2C19 293 CYP2E1 128 UGT1A1 69 UGT1A4 8 UGT1A6 34 UGT1A9 9 UGT2B7 14 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
CYP2A6 739	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
CYP2E1 970	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT1A1 254	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT1A4 80	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT1A6 141	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT1A9 121	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
UGT2B7 157	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	devoid
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	not significant
CYP2B6 1001	inducer 1573 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 1925	inducer 1573 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 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	yes [IC50 0.795 uM]
CYP2D6 1891	inhibitor 3277 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 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000PharmR.pdf#page=38 Page: 38.0	no
CYP2D6 1217	substrate 3367 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 1737	substrate 3367 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 1647	inhibitor 1626 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
AK Scientific, Inc. (AKSCI)	3973AH	http://www.aksci.com/item_detail.php?cat=3973AH
Aaron Chemicals	AR003UI4	http://www.aaronchem.com/362665-56-3
Acadechem	ACDS-056562	http://www.acadechemical.com/product/131261
Achemtek	0102-012214	http://www.achemtek.com/362665-56-3
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
BLD Pharm	BD628804	http://www.bldpharm.com/products/362665-56-3.html
BioChemPartner	BCP13114	http://www.biochempartner.com/362665-56-3-BCP13114
BioCrick	BCC1862	http://www.biocrick.com/Pitolisant-BCC1862.html
CSNpharm	CSN17352	https://www.csnpharm.com/products/pitolisant.html
Chem Scene	CS-0666	http://www.chemscene.com/362665-56-3.html
Chemspace	CSSB00015189876	https://chem-space.com/CSSB00015189876
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
abcr GmbH	AB494593	http://www.abcr.com/shop/en/AB494593

PubMed

Title	Date	PubMed
Keynote review: histamine H3 receptor antagonists reach out for the clinic.	2005 Dec	16376822
Brain histamine and schizophrenia: potential therapeutic applications of H3-receptor inverse agonists studied with BF2.649.	2007 Apr 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 Jan	17005916
Histamine H3 antagonists as wake-promoting and pro-cognitive agents.	2008	18673168
An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients.	2008 Apr	18295497
Diether derivatives of homo- or substituted piperidines as non-imidazole histamine H3 receptor ligands.	2009 Apr 15	19329325
5-hydroxyindole-2-carboxylic acid amides: novel histamine-3 receptor inverse agonists for the treatment of obesity.	2009 Jul 9	19456097
Recent advances in histamine H3 receptor antagonists/inverse agonists.	2010 Sep	20716022
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	21634396
The histamine H3 receptor: from discovery to clinical trials with pitolisant.	2011 Jun	21615387
International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.	2015 Jul	26084539

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 HYDROCHLORIDE

Official Name

English

PITOLISANT HYDROCHLORIDE [MI]

Common Name

English

PIPERIDINE, 1-(3-(3-(4-CHLOROPHENYL)PROPOXY)PROPYL)-, HYDROCHLORIDE (1:1)

Systematic Name

English

WAKIX

Brand Name

English

CIPROXIDINE

Common Name

English

PITOLISANT HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine monohydrochloride

Systematic Name

English

PITOLISANT HYDROCHLORIDE [USAN]

Common Name

English

BF-2649 HYDROCHLORIDE

Code

English

Pitolisant hydrochloride [WHO-DD]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/07/459