| 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.
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| Related Catalog |
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| 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].
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| 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].
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| References |
[1]. Atack JR, et al. Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist. J Psychopharmacol. 2011 Mar;25(3):329-44.
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