Padsevonil

Padsevonil (UCB0942) is a potent antiepileptic agent that selectively acts on presynaptic and postsynaptic targets. Padsevonil binds to synaptic vesicular protein 2 (SV2) with high affinity. Padsevonil is also a positive allosteric modulator and partial agonist of GABA_AR, with high potency against α1 and α5 receptors. Padsevonil has antiepileptic effects in a variety of rodent models^[1][2]. In Vitro:Padsevonil (0.01-30 µM) regulates GABA_AR activity through allosteric sites on the receptor in CHO cells that stably express human α1β2γ2 GABA_AR with an EC₅₀ of 138 nM^[1].
Padsevonil (0-30 µM) enhances natural GABA_AR activity in a concentration-dependent manner in primary rat neurons with an EC₅₀ of 208 nM^[1]. In Vivo:Padsevonil (0.014-181.4 mg/kg; intraperitoneal injection; single dose) has protective effects on the mouse model of acute epilepsy induced by 6Hz stimulation, acoustic stimulation and pilarine (HY-B0726A), with the ED₅₀ values of 0.16, 0.17 and 0.19 mg/kg, respectively^[2].
Padsevonil (0.14-30 mg/kg; intraperitoneal injection; single dose) has a protective effect in a rodent model of chronic epilepsy ^[2].