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Details

Stereochemistry ACHIRAL
Molecular Formula C20H22FN7O
Molecular Weight 395.4341
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MK-0777

SMILES

CCn1c(COc2c(cc3nnc(-c4ccccc4F)n3n2)C(C)(C)C)ncn1

InChI

InChIKey=QKIWQBLNTSQOLY-UHFFFAOYSA-N
InChI=1S/C20H22FN7O/c1-5-27-17(22-12-23-27)11-29-19-14(20(2,3)4)10-16-24-25-18(28(16)26-19)13-8-6-7-9-15(13)21/h6-10,12H,5,11H2,1-4H3

HIDE SMILES / InChI

Molecular Formula C20H22FN7O
Molecular Weight 395.4341
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

MK 0777 is a selective GABAA α2/3 receptor partial agonist, for potential use in the treatment of Schizophrenia, Anxiety Disorder, and Generalized Anxiety Disorder. MK-0777 is functionally selective for the α2 and α3 subunits, with virtually no activity for the α1 and α5 subunits. Therefore, MK-0777 cause less sedation, interact less with alcohol, and exhibit less abuse potential and physical dependence than benzodiazepines. Unfortunately, in clinical trials, MK-0777 has little benefit for cognitive impairments in people with schizophrenia and anxiety disorder.

Approval Year

PubMed

PubMed

TitleDatePubMed
7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activity but is not sedating in animal models.
2005 Nov 17
TPA023 [7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine], an agonist selective for alpha2- and alpha3-containing GABAA receptors, is a nonsedating anxiolytic in rodents and primates.
2006 Jan
Metabolism and disposition of a potent and selective GABA-Aalpha2/3 receptor agonist in healthy male volunteers.
2006 Jun
Cytochrome P450 3A-dependent metabolism of a potent and selective gamma-aminobutyric acid Aalpha2/3 receptor agonist in vitro: involvement of cytochrome P450 3A5 displaying biphasic kinetics.
2007 Aug
Pharmacodynamic and pharmacokinetic effects of TPA023, a GABA(A) alpha(2,3) subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers.
2007 Jun
Pharmacodynamic and pharmacokinetic effects of MK-0343, a GABA(A) alpha2,3 subtype selective agonist, compared to lorazepam and placebo in healthy male volunteers.
2008 Jan
Novel discriminative stimulus effects of TPA023B, subtype-selective gamma-aminobutyric-acid(A)/benzodiazepine modulator: comparisons with zolpidem, lorazepam, and TPA023.
2008 Jul
In vivo characterization and dynamic receptor occupancy imaging of TPA023B, an alpha 2/alpha 3/alpha 5 subtype selective gamma-aminobutyric acid-a partial agonist.
2008 Jul 15
Pharmacological Properties of DOV 315,090, an ocinaplon metabolite.
2008 Jun 13
GABA(A) receptor subtype-selective efficacy: TPA023, an alpha2/alpha3 selective non-sedating anxiolytic and alpha5IA, an alpha5 selective cognition enhancer.
2008 Spring
Subtype-selective GABA(A) receptor modulation yields a novel pharmacological profile: the design and development of TPA023.
2009
A novel operant conflict procedure using incrementing shock intensities to assess the anxiolytic and anxiogenic effects of drugs.
2009 May
GABAA receptor alpha2/alpha3 subtype-selective modulators as potential nonsedating anxiolytics.
2010
Reducing abuse liability of GABAA/benzodiazepine ligands via selective partial agonist efficacy at alpha1 and alpha2/3 subtypes.
2010 Jan
Benzodiazepine binding site occupancy by the novel GABAA receptor subtype-selective drug 7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine (TPA023) in rats, primates, and humans.
2010 Jan
Reversal of ketamine-induced working memory impairments by the GABAAalpha2/3 agonist TPA023.
2010 May 15
A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia.
2011 Mar 1
Patents

Sample Use Guides

3 mg b.i.d. or 8 mg b.i.d.
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Sat Jun 26 04:57:09 UTC 2021
Edited
by admin
on Sat Jun 26 04:57:09 UTC 2021
Record UNII
1FI3KTC550
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MK-0777
Common Name English
7-(1,1-DIMETHYLETHYL)-(6-(1-ETHYL-1H-1,2,4-TRIAZOL-5-YL)METHOXY)-3-(2-FLUOROPHENYL)-1,2,4-TRIAZOLO(4,3-B)PYRAZINE
Common Name English
1,2,4-TRIAZOLO(4,3-B)PYRIDAZINE, 7-(1,1-DIMETHYLETHYL)-6-((1-ETHYL-1H-1,2,4-TRIAZOL-5-YL)METHOXY)-3-(2-FLUOROPHENYL)-
Systematic Name English
TPA023
Code English
MK0777
Code English
TPA-023
Code English
Code System Code Type Description
WIKIPEDIA
TPA-023
Created by admin on Sat Jun 26 04:57:09 UTC 2021 , Edited by admin on Sat Jun 26 04:57:09 UTC 2021
PRIMARY
PUBCHEM
9908684
Created by admin on Sat Jun 26 04:57:09 UTC 2021 , Edited by admin on Sat Jun 26 04:57:09 UTC 2021
PRIMARY
DRUG BANK
DB12238
Created by admin on Sat Jun 26 04:57:09 UTC 2021 , Edited by admin on Sat Jun 26 04:57:09 UTC 2021
PRIMARY
CAS
252977-51-8
Created by admin on Sat Jun 26 04:57:09 UTC 2021 , Edited by admin on Sat Jun 26 04:57:09 UTC 2021
PRIMARY
EPA CompTox
252977-51-8
Created by admin on Sat Jun 26 04:57:09 UTC 2021 , Edited by admin on Sat Jun 26 04:57:09 UTC 2021
PRIMARY
FDA UNII
1FI3KTC550
Created by admin on Sat Jun 26 04:57:09 UTC 2021 , Edited by admin on Sat Jun 26 04:57:09 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
TARGET -> AGONIST
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METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION

SINGLE DOSE