252977-51-8

252977-51-8 structure

Name: TPA 023
Chemical Name: 7-tert-butyl-6-[(2-ethyl-1,2,4-triazol-3-yl)methoxy]-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine
CAS Number: 252977-51-8
Molecular Formula: C₂₀H₂₂FN₇O
Molecular Weight: 395.43300
Catalog: Signaling Pathways Membrane Transporter/Ion Channel GABA Receptor
Create Date: 2016-10-12 05:53:41
Modify Date: 2024-01-13 15:21:53
TPA 023 is a GABAA α2/α3 subtype-selective agonist, with Ki of 0.19-0.41 nM.

Name	7-tert-butyl-6-[(2-ethyl-1,2,4-triazol-3-yl)methoxy]-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine
Synonyms	unii-1fi3ktc550 mk0777 tpa-023 gtpl4327 TPA 023

Description	TPA 023 is a GABAA α2/α3 subtype-selective agonist, with Ki of 0.19-0.41 nM.
Related Catalog	Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor Signaling Pathways >> Neuronal Signaling >> GABA Receptor Research Areas >> Neurological Disease
Target	Ki: 0.19-0.41 nM (GABAA)[1]
In Vivo	TPA023 displays good receptor occupancy, when administered orally to rats. The dose of TPA023 resulting in 50% occupancy of rat brain GABAA receptors is 0.42 mg/kg, with the corresponding plasma concentration being 25 ng/mL. TPA023 is also efficacious in the mouse pentylenetetrazole-induced seizure model, providing full seizure protection at a dose of 10 mg/kg i.p. (84% occupancy), with the ED50 of 0.19-0.41 nM, for protection against tonic convulsions (1.4 mg/kg i.p.) corresponding to around 50% occupancy. TPA023 (3 mg/kg p.o. in 0.5% methyl cellulose) shows anxiolytic-like effect on rats[1]. TPA023 (0.7, 2.0, and 5 mg/kg, p.o.) blocks ketamine's cognitive-impairing ability but does not influence the behavioral symptoms of rhesus monkeys[2].
References	[1]. Atack JR. Subtype-selective GABA(A) receptor modulation yields a novel pharmacological profile: the design and development of TPA023. Adv Pharmacol. 2009;57:137-85 [2]. Castner SA, et al. Reversal of ketamine-induced working memory impairments by the GABAAalpha2/3 agonist TPA023. Biol Psychiatry. 2010 May 15;67(10):998-1001.