425377-76-0
425377-76-0 structure
- Name: TPA023B
- Chemical Name: TPA-023B
- CAS Number: 425377-76-0
- Molecular Formula: C21H15F2N5O
- Molecular Weight: 391.374
- Catalog: Signaling Pathways Membrane Transporter/Ion Channel GABA Receptor
- Create Date: 2020-01-12 00:37:01
- Modify Date: 2024-01-30 09:16:00
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TPA023B is a potent, α2/α3 subtype-selective GABAA receptor partial agonist with Ki of 2.0 and 1.8 nM, does not affect the functioning of the α1 subtype; demonstrates anxiolytic effects in rodent and primate models of anxiety, with no significant effects in ataxia and/or myorelaxation.
| Name | TPA-023B |
|---|---|
| Synonyms |
MFCD30532602
2',6-Difluoro-5'-[3-(2-hydroxy-2-propanyl)imidazo[1,2-b][1,2,4]triazin-7-yl]-2-biphenylcarbonitrile TPA-023B 2',6-Difluoro-5'-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile [1,1'-Biphenyl]-2-carbonitrile, 2',6-difluoro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]- |
| Description | TPA023B is a potent, α2/α3 subtype-selective GABAA receptor partial agonist with Ki of 2.0 and 1.8 nM, does not affect the functioning of the α1 subtype; demonstrates anxiolytic effects in rodent and primate models of anxiety, with no significant effects in ataxia and/or myorelaxation. |
|---|---|
| Related Catalog | |
| In Vitro | TPA-023B also has high affinity for α5 subtype (Ki of 1.1 nM) of human recombinant GABAA receptor, but over 1500-fold lower for the α4- and α6 containing subtypes (Ki > 1000 nM). TPA-023B also has a comparable affinity for native rat GABAA receptors in different regions of the CNS (Ki of 0.32-0.99 nM in cerebellum, spinal cord and frontal cortex)[1]. TPA-023B antagonizes the ability of chlordiazepoxide to potentiate the GABA EC20-induced current in cells expressing the α1 subtype. More specifically, 3 μM chlordiazepoxide potentiates the GABA EC20 current by 105% and this effect could be reduced to 8% in the presence of 100 nM TPA-023B[1]. |
| In Vivo | TPA-023B gives dose- and time-dependent occupancy of rat brain GABAA receptors as measured using an in vivo [3H]flumazenil binding assay, with 50% occupancy corresponding to a respective dose and plasma drug concentration of 0.09 mg/kg and 19 ng/mL[1]. TPA-023B is anxiolytic in rodent and primate (squirrel monkey) models of anxiety (elevated plus maze, fear-potentiated startle, conditioned suppression of drinking, conditioned emotional response) yet has no significant effects in rodent or primate assays of ataxia and/or myorelaxation (rotarod, chain-pulling, lever pressing), up to doses (10 mg/kg) corresponding to occupancy of greater than 99%[1]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Molecular Formula | C21H15F2N5O |
| Molecular Weight | 391.374 |
| Exact Mass | 391.124481 |
| LogP | 1.36 |
| Index of Refraction | 1.658 |