GABAA receptor modulators(Gamma-aminobutyric acid A receptor modulators), GABRA2 agonists(Gamma-aminobutyric acid A receptor alpha-2 agonists), GABRA3 agonists(Gamma-aminobutyric acid A receptor alpha-3 agonists)

+ [1]

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Anxiety Disorders

Originator Organization

Merck Sharp & Dohme Corp.

Active Organization

Merck & Co., Inc.

Inactive Organization

Merck Sharp & Dohme Corp.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Structure

Molecular FormulaC21H15F2N5O

InChIKeyPCZLQMGFNUNVOM-UHFFFAOYSA-N

CAS Registry425377-76-0

100 Clinical Results associated with TPA-023B

100 Translational Medicine associated with TPA-023B

100 Patents (Medical) associated with TPA-023B

Literatures (Medical) associated with TPA-023B

01 Feb 2021·PainQ1 · MEDICINE

The α2/α3GABAA receptor modulator TPA023B alleviates not only the sensory but also the tonic affective component of chronic pain in mice

Q1 · MEDICINE

Article

Author: Küpfer, Laura ; Neumann, Elena ; Zeilhofer, Hanns Ulrich

AbstractDiminished synaptic inhibition in the spinal dorsal horn is a major contributor to pathological pain syndromes of neuropathic or inflammatory origin. Drugs that enhance the activity of dorsal horn α2/α3GABAARs normalize exaggerated nociceptive responses in rodents with neuropathic nerve lesions or peripheral inflammation but lack most of the typical side effects of less specific GABAergic drugs. It is however still unknown whether such drugs also reduce the clinically more relevant conscious perception of pain. Here, we investigated the effects of the α2/α3GABAAR subtype-selective modulator TPA023B on the tonic aversive component of pain in mice with peripheral inflammation or neuropathy. In neuropathic mice with a chronic constriction injury of the sciatic nerve, TPA023B not only reversed hyperalgesia to tactile and heat stimuli but also was highly effective in the conditioned place preference test. In the formalin test, TPA023B not only reduced licking of the injected paw but also reversed facial pain expression scores in the mouse grimace scale assay. Taken together, our results demonstrate that α2/α3GABAA receptor subtype-selective modulators not only reduce nociceptive withdrawal responses but also alleviate the tonic aversive components of chronic pain.

01 Jul 2018·Journal of Pharmacology and Experimental TherapeuticsQ3 · MEDICINE

Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABA_A Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys

Q3 · MEDICINE

Article

Author: Tiruveedhula, V V N Phani Babu ; Duke, Angela N ; Atack, John R ; Stephen, Michael Rajesh ; Rowlett, James K ; Sieghart, Werner ; Li, Guanguan ; Cook, James M ; Platt, Donna M ; Meng, Zhiqiang ; Dawson, Gerard R ; Reynolds, David S

In nonhuman primates we tested a new set of behavioral categories for observable sedative effects using pediatric anesthesiology classifications as a basis. Using quantitative behavioral observation techniques in rhesus monkeys, we examined the effects of alprazolam and diazepam (nonselective benzodiazepines), zolpidem (preferential binding to α1 subunit-containing GABA_A receptors), HZ-166 (8-ethynyl-6-(2'-pyridine)-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester; functionally selective with relatively high intrinsic efficacy for α2 and α3 subunit-containing GABA_A receptors), MRK-696 [7-cyclobutyl-6-(2-methyl-2H-1,2,4-triazol-2-ylmethoxy)-3-(2-flurophenyl)-1,2,4-triazolo(4,3-b)pyridazine; no selectivity but partial intrinsic activity], and TPA023B 6,2'-diflouro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile; partial intrinsic efficacy and selectivity for α2, α3, α5 subunit-containing GABA_A receptors]. We further examined the role of α1 subunit-containing GABA_A receptors in benzodiazepine-induced sedative effects by pretreating animals with the α1 subunit-preferring antagonist β-carboline-3-carboxylate-t-butyl ester (βCCT). Increasing doses of alprazolam and diazepam resulted in the emergence of observable ataxia, rest/sleep posture, and moderate and deep sedation. In contrast, zolpidem engendered dose-dependent observable ataxia and deep sedation but not rest/sleep posture or moderate sedation, and HZ-166 and TPA023 induced primarily rest/sleep posture. MRK-696 induced rest/sleep posture and observable ataxia. Zolpidem, but no other compounds, significantly increased tactile/oral exploration. The sedative effects engendered by alprazolam, diazepam, and zolpidem generally were attenuated by βCCT pretreatments, whereas rest/sleep posture and suppression of tactile/oral exploration were insensitive to βCCT administration. These data suggest that α2/3-containing GABA_A receptor subtypes unexpectedly may mediate a mild form of sedation (rest/sleep posture), whereas α1-containing GABA_A receptors may play a role in moderate/deep sedation.

01 Oct 2013·NeuropsychopharmacologyQ1 · MEDICINE

Allosteric Modulation of GABAA Receptor Subtypes: Effects on Visual Recognition and Visuospatial Working Memory in Rhesus Monkeys

Q1 · MEDICINE

Article

Author: Rallapalli, Sundari K. ; Cook, James M. ; Clayton, Terry ; Biawat, Poonam ; Ator, Nancy A. ; Soto, Paul L. ; Weed, Michael R.

Non-selective positive allosteric modulators (PAMs) of GABAA receptors (GABAARs) are known to impair anterograde memory. The role of the various GABAAR subtypes in the memory-impairing effects of non-selective GABAAR PAMs has not been fully elucidated. The current study assessed, in rhesus monkeys, effects of modulation of α1, α2/3, and α5GABAARs on visual recognition and spatial working memory using delayed matching-to-sample (DMTS) and self-ordered spatial search (SOSS) procedures, respectively. The DMTS procedure (n=8) involved selecting a previously presented 'sample' image from a set of multiple images presented after a delay. The SOSS procedure (n=6) involved touching a number of boxes without repeats. The non-selective GABAAR PAM triazolam and the α1GABAA preferential PAMS zolpidem and zaleplon reduced accuracy in both procedures, whereas the α5GABAA preferential PAMs SH-053-2'F-R-CH3 and SH-053-2'F-S-CH3, and the α2/3GABAA preferential PAM TPA023B were without effects on accuracy or trial completion. The low-efficacy α5GABAAR negative allosteric modulator (NAM) PWZ-029 slightly increased only DMTS accuracy, whereas the high-efficacy α5GABAAR NAMs RY-23 and RY-24 did not affect accuracy under either procedure. Finally, the slopes of the accuracy dose-effect curves for triazolam, zolpidem, and zaleplon increased with box number in the SOSS procedure, but were equivalent across DMTS delays. The present results suggest that (1) α1GABAARs, compared with α2/3 and α5GABAARs, are primarily involved in the impairment, by non-selective GABAAR PAMs, of visual recognition and visuospatial working memory in nonhuman primates; and (2) relative cognitive impairment produced by positive modulation of GABAARs increases with number of locations to be remembered, but not with the delay for remembering.

100 Deals associated with TPA-023B

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Anxiety Disorders	Preclinical	-	Merck Sharp & Dohme Corp.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

TPA-023B

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation