TPA-023B 是一种高亲和力的口服活性的 GABA_A 受体 α2/α3 亚型 (K_i 为 0.73 nM/2 nM) 部分激动剂和 α1 亚型 (K_i 为 1.8 nM) 拮抗剂。TPA-023B 具有非镇静抗焦虑特性。

TPA-023B is a high-affinity and orally active GABA A receptor α2/α3 subtype (K i s of 0.73 nM/2 nM) partial agonist and a α1 subtype (K i of 1.8 nM) antagonist. TPA-023B has non-sedating anxiolytic-like properties.

Solid

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).
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. has not independently confirmed the accuracy of these methods. They are for reference only.

TPA-023B gives dose- and time-dependent occupancy of rat brain GABA A receptors as measured using an in vivo [H]flumazenil binding assay, with 50% occupancy corresponding to a respective dose and plasma drug concentration of 0.09 mg/kg and 19 ng/mL.
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%. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[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.