TEZAMPANEL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H21N5O2.H2O
Molecular Weight	297.3534
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.[H][C@@]12CC[C@H](CCC3=NN=NN3)C[C@]1([H])C[C@H](NC2)C(O)=O

InChI

InChIKey=LNDYQNTTYXLTNH-RTBBDAMFSA-N

InChI=1S/C13H21N5O2.H2O/c19-13(20)11-6-10-5-8(1-3-9(10)7-14-11)2-4-12-15-17-18-16-12;/h8-11,14H,1-7H2,(H,19,20)(H,15,16,17,18);1H2/t8-,9+,10-,11+;/m1./s1

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15196302 | https://www.ncbi.nlm.nih.gov/pubmed/8609884

Tezampanel, also known as LY 293558 and NGX-424, is a drug originally developed by Eli Lilly, which is a competitive antagonist of the AMPA and kainate subtypes of the ionotropic glutamate receptor family. Tezampanel was in phase II clinical trial for treatment migraine, but this study was discontinued. Also this drug has several others potential pharmacological actions, one of them is anxiety disorders

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate receptor ionotropic kainate 24 Target ID: CHEMBL2109241 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8609884	Antagonist 2778
Glutamate receptor ionotropic AMPA 41 Target ID: CHEMBL2096670 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7760975	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine 103 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15196302	Primary		Phase II 1132	Unknown Approved Use Unknown
Anxiety 267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16470401	Primary		Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
18433 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23042954	15 mg/kg single, intramuscular dose: 15 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:		TEZAMPANEL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
9396 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23042954	15 mg/kg single, intramuscular dose: 15 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:		TEZAMPANEL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23042954	15 mg/kg single, intramuscular dose: 15 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:		TEZAMPANEL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

PubMed

Title	Date	PubMed
AMPA/kainate antagonist LY293558 reduces capsaicin-evoked hyperalgesia but not pain in normal skin in humans.	1998 Nov	9821993
Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse.	2001	11077068
Differential involvement of NMDA, AMPA/kainate, and dopamine receptors in the nucleus accumbens core in the acquisition and performance of pavlovian approach behavior.	2001 Dec 1	11717381
Amygdala regulation of nucleus accumbens dopamine output is governed by the prefrontal cortex.	2001 Jan 15	11160446
Synthesis of anticonvulsive AMPA antagonists: 4-oxo-10-substituted-imidaz.	2001 May 7	11354378
Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability.	2003 Aug	12931958
Distinct contributions of glutamate receptor subtypes to cognitive set-shifting abilities in the rat.	2003 Nov	14684490
Examining the neural targets of the AMPA receptor potentiator LY404187 in the rat brain using pharmacological magnetic resonance imaging.	2005 Aug	15864556
The effect of the AMPA/kainate receptor antagonist LY293558 in a rat model of postoperative pain.	2006 Oct	17018337
Epidural tezampanel, an AMPA/kainate receptor antagonist, produces postoperative analgesia in rats.	2007 Oct	17898404
Gateways to clinical trials.	2008 Oct	19088949
Fractionating spatial memory with glutamate receptor subunit-knockout mice.	2009 Dec	19909269
Suppression of stretch reflex activity after spinal or systemic treatment with AMPA receptor antagonist NGX424 in rats with developed baclofen tolerance.	2010 Nov	20977450
A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists.	2015 Apr 15	25689173

Sample Use Guides

In Vivo Use Guide

Single Administration of: TEZAMPANEL 40 mg; TEZAMPANEL 70 mg; TEZAMPANEL 100 mg

Route of Administration: Other

In Vitro Use Guide

LY293558 (Tezampanel) had a rank order of potency of GLU(K5) > or = GLU(K5/6) approximately GLU(A2i) approximately GLU(K2/5) approximately GLU(A1i) approximately GLU(A2o) approximately GLU(A3i) approximately GLU(A1o) > or = GLU(A3o) > or = GLU(A4i) approximately GLU(A4o) and >100 microM affinity for rat cortical GABA(A) receptors. Comparison of the blockade of AMPA- vs N-methyl-D-aspartate (NMDA)-induced inward currents demonstrated that LY293558 was five-fold more potent as an antagonist at AMPA vs NMDA receptors in vitro.

Name

Type

Language

TEZAMPANEL

Official Name

English

LY293558

Code

English

TEZAMPANEL [USAN]

Common Name

English

(3S,4aR,6R,8aR)-6-[2-(1H-Tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid monohydrate

Common Name

English

TEZAMPANEL HYDRATE

Common Name

English

3-ISOQUINOLINECARBOXYLIC ACID, DECAHYDRO-6-(2-(1H-TETRAZOL-5-YL)ETHYL)-, MONOHYDRATE, (3S,4AR,6R,8AR)-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47795