TEZAMPANEL ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H21N5O2
Molecular Weight	279.3381
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=ZXFRFPSZAKNPQQ-YTWAJWBKSA-N

InChI=1S/C13H21N5O2/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)/t8-,9+,10-,11+/m1/s1

HIDE SMILES / InChI

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
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
LY293558, an AMPA glutamate receptor antagonist, prevents and reverses levodopa-induced motor alterations in Parkinsonian rats.	2001 Oct	11668589
LY-293558. Eli Lilly & Co.	2001 Sep	11717815
Dissociable effects of antagonism of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell on cocaine-seeking behavior.	2001 Sep	11522463
AMPA receptor antagonist LY293558 reverses preproenkephalin mRNA overexpression in the striatum of 6-OHDA-lesioned-rats treated with L-dopa.	2002 Dec	12473092
Extradural compression of sensorimotor cortex: a useful model for studies on ischemic brain damage and neuroprotection.	2002 Jan	11852980
Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.	2002 Jul	12131120
Effect of bilateral hypogastric nerve transection on voiding dysfunction in rats with spinal cord injury.	2002 May	12009771
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
Direct interactions between the basolateral amygdala and nucleus accumbens core underlie cocaine-seeking behavior by rats.	2004 Aug 11	15306650
LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine.	2004 Jul	15196302
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	15857706
Histaminergic modulation of excitatory synaptic transmission in the rat basolateral amygdala.	2005	15730874
Examining the neural targets of the AMPA receptor potentiator LY404187 in the rat brain using pharmacological magnetic resonance imaging.	2005 Aug	15864556
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	15930507
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	16470401
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	16039722
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
Regulation of AMPA receptors in spinal nociception.	2010 Jan 21	20092646
Suppression of stretch reflex activity after spinal or systemic treatment with AMPA receptor antagonist NGX424 in rats with developed baclofen tolerance.	2010 Nov	20977450
Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury.	2010 Nov	20662840
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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:01:12 GMT 2023` Edited by `admin` on `Fri Dec 15 16:01:12 GMT 2023`
Record UNII	GA36S2O9C2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TEZAMPANEL ANHYDROUS

Common Name

English

NGX424

Code

English

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

Common Name

English

NGX-424

Code

English

(3S,4AS,6R,8AS)-6-(2-(1H-TETRAZOL-5-YL)ETHYL)DECAHYDROISOQUINOLINE-3-CARBOXYLIC ACID

Common Name

English

LY-293558

Code

English

LY-293,558

Code

English

tezampanel [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47795