TRAXOPRODIL MESYLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H25NO3.CH4O3S.3H2O
Molecular Weight	477.569
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.O.CS(O)(=O)=O.C[C@@H]([C@@H](O)C1=CC=C(O)C=C1)N2CCC(O)(CC2)C3=CC=CC=C3

InChI

InChIKey=LUILKELNVBKKTG-ZOZJKLBQSA-N

InChI=1S/C20H25NO3.CH4O3S.3H2O/c1-15(19(23)16-7-9-18(22)10-8-16)21-13-11-20(24,12-14-21)17-5-3-2-4-6-17;1-5(2,3)4;;;/h2-10,15,19,22-24H,11-14H2,1H3;1H3,(H,2,3,4);3*1H2/t15-,19+;;;;/m0..../s1

HIDE SMILES / InChI

Molecular Formula	CH4O3S
Molecular Weight	96.106
Charge	0
Count

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

Molecular Formula	C20H25NO3
Molecular Weight	327.4174
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10785463
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11249721

Traxoprodil (CP-101,606) is a potent, selective N-Methyl-D-aspartate (NMDA) receptor (NR2B subunit) antagonist under development by Pfizer for its potential as a neuroprotectant in head injury and neurodegenerative disease. It is in phase II trials in the US and in phase I in Japan for the potential treatment of head injury, such as, Depressive Disorder, Major and Parkinson's Disease. CP-101,606 does not protect against glutamate-induced neurotoxicity in cultured cerebellar neurons, up to a dose of 10 uM. These results are consistent with CP-101,606 being a potent NMDA antagonist, selective for the type of NMDA receptor associated with the hippocampus. Some further investigation revealed that CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor subunit epsilon 2 13 Target ID: CHEMBL311 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10785463	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Major depressive disorder 173 Sources: https://clinicaltrials.gov/ct2/show/NCT00163059	Palliative		Phase II 1132	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://clinicaltrials.gov/ct2/show/NCT00163085	Palliative		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
674 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16984212	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		TRAXOPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
246 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16984212	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:		TRAXOPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
1370 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16984212	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		TRAXOPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
856 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16984212	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:		TRAXOPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16984212	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		TRAXOPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16984212	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:		TRAXOPRODIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
300 mg single, oral Highest studied dose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://pubmed.ncbi.nlm.nih.gov/16984212 Page: p.995	healthy, ADULT n = 11 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/16984212 Page: p.995	Sources: https://pubmed.ncbi.nlm.nih.gov/16984212 Page: p.995
0.75 mg/kg 1 times / hour multiple, intravenous Highest studied dose Dose: 0.75 mg/kg, 1 times / hour Route: intravenous Route: multiple Dose: 0.75 mg/kg, 1 times / hour Co-administed with:: levodopa(25mg, was administered orally) Carbidopa Sources: https://pubmed.ncbi.nlm.nih.gov/18759356 Page: p.5, 13	unhealthy, ADULT n = 12 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/18759356 Page: p.5, 13	Other AEs: Abnormal thinking... Other AEs: Abnormal thinking (83.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/18759356 Page: p.5, 13

AEs

AE	Significance	Dose	Population
Abnormal thinking	83.3%	0.75 mg/kg 1 times / hour multiple, intravenous Highest studied dose Dose: 0.75 mg/kg, 1 times / hour Route: intravenous Route: multiple Dose: 0.75 mg/kg, 1 times / hour Co-administed with:: levodopa(25mg, was administered orally) Carbidopa Sources: https://pubmed.ncbi.nlm.nih.gov/18759356 Page: p.5, 13	unhealthy, ADULT n = 12 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/18759356 Page: p.5, 13

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY100066	https://www.001chemical.com/chem/search?q=DY100066
1PlusChem LLC	1P007MWR	https://www.1pchem.com/search?query=1P007MWR
AK Scientific	X9873	https://aksci.com/item_detail.php?cat=X9873
Achemo Scientific Limited	AC-73955	http://www.achemo.com/search/?Keyword=AC-73955
Alfa Chemistry	7452	http://www.alfa-chemistry.com/search.aspx?q=7452
Alfa Chemistry	AFI134234121	http://www.alfa-chemistry.com/search.aspx?q=AFI134234121
Ambeed	A294642	http://www.ambeed.com/search/Search.html?keyword=A294642
Angene	AGN-PC-0QJAG3	http://www.angenechemical.com/productshow/AGN-PC-0QJAG3.html
AstaTech	11041	http://astatechinc.com/CPSResult.php?CRNO=11041
AstaTech	38019	http://astatechinc.com/CPSResult.php?CRNO=38019
AstaTech	41534	http://astatechinc.com/CPSResult.php?CRNO=41534
AstaTech	H11008	http://astatechinc.com/CPSResult.php?CRNO=H11008
Axon MedChem	1406	https://www.axonmedchem.com/product/1406
Axon MedChem	2254	https://www.axonmedchem.com/product/2254
BOC Sciences	134234-12-1	http://www.bocsci.com/description.asp?cas=134234-12-1
Capot Chemical	35570	https://www.capotchem.com/search.do?q=35570
Chem Scene	CS-W018847	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-W018847
Combi-Blocks	QJ-5465	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-5465
Combi-Blocks	QP-9711	http://www.combi-blocks.com/cgi-bin/find.cgi?QP-9711
KeyOrganics	8Y-7002	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=8Y-7002
KeyOrganics	DS-5988	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=DS-5988
KeyOrganics	ES-0057	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=ES-0057
Matrix Scientific	65361	http://www.matrixscientific.com/065361.html
MedChem Express	HY-W018061	https://www.medchemexpress.com/search.html?q=HY-W018061&ft=&fa=&fp=
MolPort	MolPort-019-906-294	https://www.molport.com/shop/molecule-link/MolPort-019-906-294
MolPort	MolPort-020-313-405	https://www.molport.com/shop/molecule-link/MolPort-020-313-405
MolPort	MolPort-023-219-113	https://www.molport.com/shop/molecule-link/MolPort-023-219-113
Molcore	MC100066	http://www.molcore.com/CatMC100066.html
Molnova	M11373	https://www.molnova.com/en/serch-list.html?keywords=M11373
Molnova	M12949	https://www.molnova.com/en/serch-list.html?keywords=M12949
MuseChem	M111413	https://www.musechem.com/product/M111413.html
Oakwood	213429	http://www.oakwoodchemical.com/ProductsList.aspx?txtSearch=213429
PepTech	RC921-1	http://www.peptechcorp.com/products/productSearch.asp?searchString=RC921-1
ShangHai Biochempartner	BCP13195	http://www.biochempartner.com/search_BCP13195
Toronto Research Chemicals	T010120	https://www.trc-canada.com/product-detail/?CatNum=T010120
Wonderchem	WD02XY6	http://www.wonder-chem.com/search.html?text=WD02XY6
Wonderchem	WD053T0	http://www.wonder-chem.com/search.html?text=WD053T0
eMolecules	168696620	https://orderbb.emolecules.com/search/#?query=168696620
eMolecules	205720138	https://orderbb.emolecules.com/search/#?query=205720138
eMolecules	36027883	https://orderbb.emolecules.com/search/#?query=36027883
eMolecules	36367067	https://orderbb.emolecules.com/search/#?query=36367067
eMolecules	44786232	https://orderbb.emolecules.com/search/#?query=44786232
eNovation Chemicals	D496620	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D496620&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7963903866	https://mcule.com/MCULE-7963903866/
mcule	MCULE-7999494180	https://mcule.com/MCULE-7999494180/

PubMed

Title	Date	PubMed
		252160863
Metabolism, pharmacokinetics, and excretion of a highly selective N-methyl-D-aspartate receptor antagonist, traxoprodil, in human cytochrome P450 2D6 extensive and poor metabolizers.	2003 Jan	12485956
Gateways to clinical trials.	2004 Apr	15148527
Characterization of N-methyl-D-aspartate receptor subunits involved in acute ammonia toxicity.	2004 Jan	12971910
Role of NMDA receptor subtypes in the induction of catalepsy and increase in Fos protein expression after administration of haloperidol.	2004 Jun 11	15140647
Absolute oral bioavailability of traxoprodil in cytochrome P450 2D6 extensive and poor metabolisers.	2006	16984212
The phencyclidine-like discriminative stimulus effects and reinforcing properties of the NR2B-selective N-methyl-D-aspartate antagonist CP-101 606 in rats and rhesus monkeys.	2007 Dec	17989511
Effects of a NR2B selective NMDA glutamate antagonist, CP-101,606, on dyskinesia and Parkinsonism.	2008 Oct 15	18759356
Innovative approaches to treatment - refractory depression: The ketamine story.	2010 Apr	20838494
Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic nucleus is linked to rapid activation of the NR2B subunit of N-methyl-D-aspartate receptors.	2010 Aug	20673310

Patents

Sample Use Guides

In Vivo Use Guide

CP 101,606 (TRAXOPRODIL) was administered at 0.25 mg/kg/hr for 2 hours followed by 0.12 mg/kg/hr for 2 hours, targeting a minimum plasma concentration of 60 ng/ml. “High dose” CP 101,606 was administered at 0.75 mg/kg/hr for 2 hours and then at 0.36 mg/kg/hr for 2 hours, targeting a minimum plasma concentration of 200 ng/ml. Matching placebo infusions were administered the control day. The study drug (CP-101,606 or placebo) were infused at a same infusion rates for each subject via a dedicated intravenous line.

Route of Administration: Intravenous

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:36:24 UTC 2023` Edited by `admin` on `Fri Dec 15 15:36:24 UTC 2023`
Record UNII	BD2A56I30W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRAXOPRODIL MESYLATE

Official Name

English

1-PIPERIDINEETHANOL, 4-HYDROXY-.ALPHA.-(4-HYDROXYPHENYL)-.BETA.-METHYL-4-PHENYL-, (.ALPHA.S,.BETA.S)-, METHANESULFONATE, HYDRATE (1:1:3)

Common Name

English

CP-101606-27

Code

English

TRAXOPRODIL MESILATE HYDRATE

Common Name

English

TRAXOPRODIL MESILATE TRIHYDRATE

Common Name

English

(αS,βS)-4-Hydroxy-α-(P-hydroxyphenyl)-β-methyl-4-phenyl-1-piperidineethanol methanesulfonate (salt), trihydrate

Common Name

English

TRAXOPRODIL MESYLATE TRIHYDRATE

Common Name

English

Traxoprodil mesilate hydrate [WHO-DD]

Common Name

English

CP-101,606-27

Code

English

TRAXOPRODIL MESYLATE [USAN]

Common Name

English

1-PIPERIDINEETHANOL, 4-HYDROXY-.ALPHA.-(4-HYDROXYPHENYL)-.BETA.-METHYL-4-PHENYL-, (S-(R*,R*))-, METHANESULFONATE (SALT), TRIHYDRATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29707