TPA-023

Overview

TPA-023 (MK-0777) is an anxiolytic drug with a novel chemical structure, which is used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. It is a mixed, subtype-selective ligand of the benzodiazepine site of α1, α2, α3, and α5-containing GABAA receptors, where it acts as a partial agonist at benzodiazepine sites of the α2 and α3-containing subtypes, but as a silent antagonist at α1 and α5-containing subtypes. It has primarily anxiolytic and anticonvulsant effects in animal tests, but with no sedative effects even at 50 times the effective anxiolytic dose.[1][2][3] WP

In human trials on healthy volunteers, TPA-023 was comparable to lorazepam, but lacked negative effects on cognition, memory, alertness or coordination seen with the latter drug. In Phase II trials, the compound was significantly superior to placebo without inducing sedation. The clinical development was halted due to preclinical toxicity (cataract) in long term dosing studies. TPA-023 is well absorbed following oral administration and extensively metabolised by the liver, with a half-life of 6.7 hours. The main enzyme involved in its metabolism is CYP3A4, with some contribution by CYP3A5.[4–8] WP

Chemistry

Formula

C20H22FN7O PC

CAS number

252977-51-8 PC

Molar mass (g/mol)

395.4 PC

IUPAC name (computed by PubChem)

7-tert-butyl-6-[(2-ethyl-1,2,4-triazol-3-yl)methoxy]-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine PC

SMILES

CCN1C(=NC=N1)COC2=NN3C(=NN=C3C4=CC=CC=C4F)C=C2C(C)(C)C PC

InChIKey

QKIWQBLNTSQOLY-UHFFFAOYSA-N PC

PubChem CID

9908684

IUPAC name

7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Kohut SJ, Ator NA. Novel discriminative stimulus effects of TPA023B, subtype-selective gamma-aminobutyric-acid(A)/benzodiazepine modulator: comparisons with zolpidem, lorazepam, and TPA023. Pharmacology, Biochemistry, and Behavior. July 2008. doi:10.1016/j.pbb.2008.02.019 · PMID 18395780 · PMC3010402
2. Journal / agency Carling RW, Madin A, Guiblin A, Russell MG, Moore KW, Mitchinson A, Sohal B, Pike A, Cook SM, Ragan IC, McKernan RM, Quirk K, Ferris P, Marshall G, Thompson SA, Wafford KA, Dawson GR, Atack JR, Harrison T, Castro JL, Street LJ. 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. Journal of Medicinal Chemistry. November 2005. doi:10.1021/jm058034a · PMID 16279764
3. Journal / agency Atack JR, Wafford KA, Tye SJ, Cook SM, Sohal B, Pike A, Sur C, Melillo D, Bristow L, Bromidge F, Ragan I, Kerby J, Street L, Carling R, Castro JL, Whiting P, Dawson GR, McKernan RM. 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. The Journal of Pharmacology and Experimental Therapeutics. January 2006. doi:10.1124/jpet.105.089920 · PMID 16183706
4. Journal / agency de Haas SL, de Visser SJ, van der Post JP, de Smet M, Schoemaker RC, Rijnbeek B, Cohen AF, Vega JM, Agrawal NG, Goel TV, Simpson RC, Pearson LK, Li S, Hesney M, Murphy MG, van Gerven JM. Pharmacodynamic and pharmacokinetic effects of TPA023, a GABA(A) alpha(2,3) subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers. Journal of Psychopharmacology. June 2007. doi:10.1177/0269881106072343 · PMID 17092968
5. Journal / agency Möhler H. The rise of a new GABA pharmacology. Neuropharmacology. June 2011. doi:10.1016/j.neuropharm.2010.10.020 · PMID 21035473
6. Journal / agency Atack JR. GABA(A) receptor subtype-selective efficacy: TPA023, an alpha2/alpha3 selective non-sedating anxiolytic and alpha5IA, an alpha5 selective cognition enhancer. CNS Neuroscience & Therapeutics. 2008. doi:10.1111/j.1527-3458.2007.00034.x · PMID 18482097 · PMC6494020
7. Journal / agency Polsky-Fisher SL, Vickers S, Cui D, Subramanian R, Arison BH, Agrawal NG, Goel TV, Vessey LK, Murphy MG, Lasseter KC, Simpson RC, Vega JM, Rodrigues AD. Metabolism and disposition of a potent and selective GABA-Aalpha2/3 receptor agonist in healthy male volunteers. Drug Metabolism and Disposition. June 2006. doi:10.1124/dmd.105.008193 · PMID 16510541
8. Journal / agency Ma B, Polsky-Fisher SL, Vickers S, Cui D, Rodrigues AD. 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. Drug Metabolism and Disposition. August 2007. doi:10.1124/dmd.107.014753 · PMID 17460031

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.