TRAXOPRODIL

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H25NO3
Molecular Weight	327.4174
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

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

InChI

InChIKey=QEMSVZNTSXPFJA-HNAYVOBHSA-N

InChI=1S/C20H25NO3/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/h2-10,15,19,22-24H,11-14H2,1H3/t15-,19+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C20H25NO3
Molecular Weight	327.4174
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

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	Antagonist 2,778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Major depressive disorder 173	Palliative		Phase II 1,132	Unknown
Parkinson's disease 226	Palliative		Phase II 1,132	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
674 ng/mL	300 mg single, oral		TRAXOPRODIL plasma	Homo sapiens
246 ng/mL	100 mg single, intravenous		TRAXOPRODIL plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
1370 ng × h/mL	300 mg single, oral		TRAXOPRODIL plasma	Homo sapiens
856 ng × h/mL	100 mg single, intravenous		TRAXOPRODIL plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.5 h	300 mg single, oral		TRAXOPRODIL plasma	Homo sapiens
3.68 h	100 mg single, intravenous		TRAXOPRODIL plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
300 mg single, oral Highest studied dose	healthy, ADULT
0.75 mg/kg 1 times / hour multiple, intravenous Highest studied dose	unhealthy, ADULT	Other AEs: Abnormal thinking...

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AEs

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AE	Significance	Dose	Population
Abnormal thinking	83.3%	0.75 mg/kg 1 times / hour multiple, intravenous Highest studied dose	unhealthy, ADULT

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Sourcing

Sourcing

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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
Achemo Scientific Limited	AC-73955	http://www.achemo.com/search/?Keyword=AC-73955
AK Scientific	X9873	https://aksci.com/item_detail.php?cat=X9873
Alfa Chemistry	7452	http://www.alfa-chemistry.com/search.aspx?q=7452

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PubMed

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Title	Date	PubMed
		252160863
The effect of the selective NMDA receptor antagonist traxoprodil in the treatment of traumatic brain injury.	2005 Dec	16379581
Absolute oral bioavailability of traxoprodil in cytochrome P450 2D6 extensive and poor metabolisers.	2006	16984212
Metabolism, distribution and excretion of a selective N-methyl-D-aspartate receptor antagonist, traxoprodil, in rats and dogs.	2007 Aug	17496205
Effects of a NR2B selective NMDA glutamate antagonist, CP-101,606, on dyskinesia and Parkinsonism.	2008 Oct 15	18759356

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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
Record UNII	UTC046R5HM
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRAXOPRODIL

Official Name

English

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

Common Name

English

CP-101606

Code

English

traxoprodil [INN]

Common Name

English

(.ALPHA.S,.BETA.S)-4-HYDROXY-.ALPHA.-(P-HYDROXYPHENYL)-.BETA.-METHYL-4-PHENYL-1-PIPERIDINEETHANOL

Common Name

English

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Classification Tree

Code System

Code

Agent Affecting Cardiovascular System

NCI_THESAURUS

C29707

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Code System

Code

Type

Description

NCI_THESAURUS

C87769

PRIMARY

INN

8053

PRIMARY

SMS_ID

300000034379

PRIMARY

FDA UNII

UTC046R5HM

PRIMARY

EPA CompTox

DTXSID90158605

PRIMARY

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Related Record

Type

Details


					8E4LAA4357

CYTOCHROME P450 2D6

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

MAJOR


					UTC046R5HM

TRAXOPRODIL

EXCRETED UNCHANGED

Comments:

IN EXTENSIVE METABOLIZERS

Qualification:

FECAL

Amount:

1.11 % (average)
of Administered Dose


					43Q7J075IH

GLUTAMATE RECEPTOR IONOTROPIC, NMDA 2B

TARGET -> INHIBITOR

Amount:


					BD2A56I30W

TRAXOPRODIL MESYLATE

SALT/SOLVATE -> PARENT


					UTC046R5HM

TRAXOPRODIL

EXCRETED UNCHANGED

Comments:

IN POOR METABOLIZERS

Qualification:

URINE

Amount:

48.4 % (average)
of Administered Dose

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Related Record

Type

Details


					10DO3K28LK

3-METHOXYTRAXOPRODIL

METABOLITE -> PARENT

Comments:

IN EXTENSIVE METABOLIZERS

Qualification:

FECAL

Amount:

1.11 % [0.74 to 1.48] (average)
of Administered Dose


					N6Z8D6O9FV

(1S,2S)-1-(4-HYDROXYPHENYL)-2-(4-HYDROXY-4-PHENYL-1-PIPERIDINYL)PROPYL .BETA.-D-GLUCOPYRANOSIDURONIC ACID

METABOLITE -> PARENT

Comments:

IN POOR METABOLIZERS AT 6H

Qualification:

PLASMA

Amount:

2 % [1.9 to 2.1] (average)


					YP9FAX272T

(.ALPHA.S,.BETA.S)-4-HYDROXY-.ALPHA.-(3-METHOXY-4-(SULFOOXY)PHENYL)-.BETA.-METHYL-4-PHENYL-1-PIPERIDINEETHANOL

METABOLITE -> PARENT

Comments:

IN EXTENSIVE METABOLIZERS AT 6H

Qualification:

PLASMA

Amount:

36.4 % [33.1 to 39.7] (average)


					QFG40ZGB0F

.BETA.-D-GLUCOPYRANOSIDURONIC ACID, 4-((1S,2S)-1-HYDROXY-2-(4-HYDROXY-4-PHENYL-1-PIPERIDINYL)PROPYL)-2-METHOXYPHENYL

METABOLITE -> PARENT

Comments:

IN EXTENSIVE METABOLIZERS AT 6H

Qualification:

PLASMA

Amount:

27.9 % [25.2 to 30.6] (average)


					QFG40ZGB0F

.BETA.-D-GLUCOPYRANOSIDURONIC ACID, 4-((1S,2S)-1-HYDROXY-2-(4-HYDROXY-4-PHENYL-1-PIPERIDINYL)PROPYL)-2-METHOXYPHENYL

METABOLITE -> PARENT

Comments:

IN EXTENSIVE METABOLIZERS

Qualification:

URINE

Amount:

8.83 % [8.05 to 9.61] (average)
of Administered Dose

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Related Record

Type

Details


					UTC046R5HM

TRAXOPRODIL

ACTIVE MOIETY

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Name	Property Type	Amount	Parameters
Biological Half-life	PHARMACOKINETIC	2.8 hours [2.1 to 3.5] (average)	SINGLE DOSE 50 mg (average) INTRAVENOUS ADMINISTRATION IN CYP2D6 PHENOTYPE: EXTENSIVE METABOLIZERS

Tmax	PHARMACOKINETIC	2 hours (average)	SINGLE DOSE 50 mg (average) INTRAVENOUS ADMINISTRATION IN CYP2D6 PHENOTYPE: EXTENSIVE METABOLIZERS

Tmax	PHARMACOKINETIC	2.5 hours [2 to 3] (average)	IN CYP2D6 PHENOTYPE: POOR METABOLIZERS INTRAVENOUS ADMINISTRATION SINGLE DOSE 50 mg (average)

Biological Half-life	PHARMACOKINETIC	26.9 hours [24.5 to 29.3] (average)	SINGLE DOSE 50 mg (average) IN CYP2D6 PHENOTYPE: POOR METABOLIZERS INTRAVENOUS ADMINISTRATION

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2