MIDAFOTEL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H15N2O5P
Molecular Weight	250.1889
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)[C@H]1CN(C\C=C\P(O)(O)=O)CCN1

InChI

InChIKey=VZXMZMJSGLFKQI-ABVWVHJUSA-N

InChI=1S/C8H15N2O5P/c11-8(12)7-6-10(4-2-9-7)3-1-5-16(13,14)15/h1,5,7,9H,2-4,6H2,(H,11,12)(H2,13,14,15)/b5-1+/t7-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800002722 | https://www.ncbi.nlm.nih.gov/pubmed/2166255

Midafotel (CPPene; SDZ EAA 494) is a selective competitive antagonist at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. It was originally designed as a potential therapy for excitotoxicity, epilepsy or neuropathic pain. Midafotel had been in phase III clinical trials by Novartis for the treatment of brain injury. However, this research has been discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate NMDA receptor 46 Target ID: CHEMBL1907608 Sources: http://adisinsight.springer.com/drugs/800002722 \| https://www.ncbi.nlm.nih.gov/pubmed/2166255 \| https://www.ncbi.nlm.nih.gov/pubmed/12787951	Antagonist 2778		40.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Brain injuries 1 Sources: http://adisinsight.springer.com/drugs/800002722	Primary		Phase III 656	Unknown Approved Use Unknown
Cognition disorders 21 Sources: http://adisinsight.springer.com/drugs/800002722	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
199 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/8269915	1000 mg 2 times / day multiple, oral dose: 1000 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MIDAFOTEL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20 h REVIEW https://pubmed.ncbi.nlm.nih.gov/8269915	1000 mg 2 times / day multiple, oral dose: 1000 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MIDAFOTEL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg single, intravenous (unknown) Highest studied dose Dose: 50 mg Route: intravenous Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8740048	healthy n = 9 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/8740048	Sources: https://pubmed.ncbi.nlm.nih.gov/8740048
25 mg 2 times / day multiple, intravenous (unknown) Overdose Dose: 25 mg, 2 times / day Route: intravenous Route: multiple Dose: 25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8740048	healthy n = 9 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/8740048	Sources: https://pubmed.ncbi.nlm.nih.gov/8740048

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34554	https://www.001chemical.com/chem/search?q=DY34554
Alfa Chemistry	ACM117414741	http://www.alfa-chemistry.com/search.aspx?q=ACM117414741
ApexBio Technology	B6665	https://www.apexbt.com/catalogsearch/result/?q=B6665
BOC Sciences	117414-74-1	http://www.bocsci.com/description.asp?cas=117414-74-1
BOC Sciences	137424-80-7	http://www.bocsci.com/description.asp?cas=137424-80-7
Chemspace	CSC009881808	https://chem-space.com/CSC009881808
Chemspace	CSC020587528	https://chem-space.com/CSC020587528
Chemspace	CSC037152683	https://chem-space.com/CSC037152683
Enamine	BBV-103758289	http://www.enaminestore.com/catalog/BBV-103758289
Enamine	BBV-77845118	http://www.enaminestore.com/catalog/BBV-77845118
Enamine	BBV-78163655	http://www.enaminestore.com/catalog/BBV-78163655
Molcore	MC34554	http://www.molcore.com/CatMC34554.html
Synchem UG and Co KG	un219	https://www.synchem.de/?s=un219&post_type=product
Tetrahedron	TS62819	http://www.thsci.com/search.do?q=TS62819
Tocris	1265	https://www.tocris.com/search.php?Type=QuickSearch&Value=1265
Toronto Research Chemicals	C781465	https://www.trc-canada.com/product-detail/?CatNum=C781465
Wonderchem	WD04TW4	http://www.wonder-chem.com/search.html?text=WD04TW4
eMolecules	29702999	https://orderbb.emolecules.com/search/#?query=29702999
eMolecules	92298049	https://orderbb.emolecules.com/search/#?query=92298049
mcule	MCULE-5048138957	https://mcule.com/MCULE-5048138957/

PubMed

Title	Date	PubMed
Blockade of hindbrain NMDA receptors containing NR2 subunits increases sucrose intake.	2009 Apr	19193935
Pharmacological characterization of harmaline-induced tremor activity in mice.	2009 Aug 15	19497322
Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors.	2011 Aug	21562094
An examination of NMDA receptor contribution to conditioned responding evoked by the conditional stimulus effects of nicotine.	2011 Jan	20859617

Patents

Sample Use Guides

In Vivo Use Guide

Midafotel was administered either as single doses at a dose range of 1-50 mg, or as multiple doses over the course of 1 week at doses of 25 mg once or twice daily.

Route of Administration: Oral

In Vitro Use Guide

Midafotel (d-CPPene) strongly inhibited the frequency of spontaneous epileptiform discharges. This effect was concentration-dependent. Epileptiform discharges were reduced up to 70% at a concentration of 0.1 uM and were completely blocked at a concentration of 0.3 uM in the rat cortical wedge preparation. d-CPPene inhibited in concentration-dependent manner NMDA-induced depolarisations. A concentration of 0.1 uM that blocked 70% of spontaneous discharges inhibited 60% of depolarisations induced by NMDA. A concentration of 1 uM completely blocked NMDA-induced depolarisations.

Name

Type

Language

MIDAFOTEL

Official Name

English

SDZ-EAA-494

Code

English

(R)-4-((E)-3-PHOSPHONOPROP-2-ENYL)PIPERAZINE-2-CARBOXYLIC ACID

Systematic Name

English

4-(3-PHOSPHONO-2-PROPENYL)-2-PIPERAZINECARBOXYLIC ACID, (R-(E))

Common Name

English

SDZ EAA 494

Code

English

midafotel [INN]

Common Name

English

Midafotel [WHO-DD]

Common Name

English

Classification Tree Code System Code

WIKIPEDIA

NMDA receptor antagonist

Created by admin on Fri Dec 15 15:57:16 GMT 2023 , Edited by admin on Fri Dec 15 15:57:16 GMT 2023

Code System Code Type Description

INN

7736