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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 of TEZAMPANEL

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

HIDE SMILES / InChI
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
Molecular Formula C13H21N5O2
Molecular Weight 279.3381
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

CNS Penetrant
2554
Curator's Comment: Known to be CNS penetrant in rat. Human data not available

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
Antagonist
2778
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

PubMed

TitleDatePubMed
AMPA/kainate antagonist LY293558 reduces capsaicin-evoked hyperalgesia but not pain in normal skin in humans.
1998 Nov
Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse.
2001
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
Amygdala regulation of nucleus accumbens dopamine output is governed by the prefrontal cortex.
2001 Jan 15
Synthesis of anticonvulsive AMPA antagonists: 4-oxo-10-substituted-imidaz.
2001 May 7
LY293558, an AMPA glutamate receptor antagonist, prevents and reverses levodopa-induced motor alterations in Parkinsonian rats.
2001 Oct
LY-293558. Eli Lilly & Co.
2001 Sep
Dissociable effects of antagonism of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell on cocaine-seeking behavior.
2001 Sep
AMPA receptor antagonist LY293558 reverses preproenkephalin mRNA overexpression in the striatum of 6-OHDA-lesioned-rats treated with L-dopa.
2002 Dec
Extradural compression of sensorimotor cortex: a useful model for studies on ischemic brain damage and neuroprotection.
2002 Jan
Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.
2002 Jul
Effect of bilateral hypogastric nerve transection on voiding dysfunction in rats with spinal cord injury.
2002 May
Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability.
2003 Aug
Distinct contributions of glutamate receptor subtypes to cognitive set-shifting abilities in the rat.
2003 Nov
Direct interactions between the basolateral amygdala and nucleus accumbens core underlie cocaine-seeking behavior by rats.
2004 Aug 11
LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine.
2004 Jul
Supraspinal and spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D-aspartate glutamatergic control of the micturition reflex in the urethane-anesthetized rat.
2005
Histaminergic modulation of excitatory synaptic transmission in the rat basolateral amygdala.
2005
Examining the neural targets of the AMPA receptor potentiator LY404187 in the rat brain using pharmacological magnetic resonance imaging.
2005 Aug
AMPA/kainate, NMDA, and dopamine D1 receptor function in the nucleus accumbens core: a context-limited role in the encoding and consolidation of instrumental memory.
2005 May-Jun
In vitro and in vivo studies in rats with LY293558 suggest AMPA/kainate receptor blockade as a novel potential mechanism for the therapeutic treatment of anxiety disorders.
2006 Apr
Reflexes evoked by electrical stimulation of afferent axons in the pudendal nerve under empty and distended bladder conditions in urethane-anesthetized rats.
2006 Jan 15
The effect of the AMPA/kainate receptor antagonist LY293558 in a rat model of postoperative pain.
2006 Oct
Epidural tezampanel, an AMPA/kainate receptor antagonist, produces postoperative analgesia in rats.
2007 Oct
Gateways to clinical trials.
2008 Oct
Fractionating spatial memory with glutamate receptor subunit-knockout mice.
2009 Dec
Regulation of AMPA receptors in spinal nociception.
2010 Jan 21
Suppression of stretch reflex activity after spinal or systemic treatment with AMPA receptor antagonist NGX424 in rats with developed baclofen tolerance.
2010 Nov
Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury.
2010 Nov
A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists.
2015 Apr 15

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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:20:49 GMT 2023
Edited
by admin
on Fri Dec 15 17:20:49 GMT 2023
Record UNII
6XN50U405Y
Record Status Validated (UNII)
Record Version
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Name Type Language
TEZAMPANEL
USAN  
USAN  
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
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C77316
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
MESH
C082309
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
USAN
RR-94
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
ChEMBL
CHEMBL14935
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
EPA CompTox
DTXSID50953714
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
DRUG BANK
DB06354
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
CAS
317819-68-4
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
SMS_ID
300000034402
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
PUBCHEM
23725095
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
FDA UNII
6XN50U405Y
Created by admin on Fri Dec 15 17:20:49 GMT 2023 , Edited by admin on Fri Dec 15 17:20:49 GMT 2023
PRIMARY
Related Record Type Details
Structure of TEZAMPANEL ANHYDROUS
PARENT -> SALT/SOLVATE
Structure of TEZAMPANEL ANHYDROUS
ANHYDROUS->SOLVATE
Related Record Type Details
Structure of TEZAMPANEL ANHYDROUS
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