Ocinaplon

Ocinaplon (DOV 273547) is an orally active positive allosteric modulator of GABA_A receptor, with an EC₅₀ ranging from 3.07 μM (α1β2γ2 subtype) to 10.03 μM (α1β2γ3 subtype). Ocinaplon enhances GABA-stimulated chloride currents across multiple GABA_A receptor subtypes, with varying potency between different subtypes. Ocinaplon exerts anxiolytic and anticonvulsant effects, and causes motor impairment at high doses. Ocinaplon can be used for research on generalized anxiety disorder^[1][2]. IC50 & Target:GABAA receptor^[1] In Vitro:Ocinaplon acts as a low-affinity partial agonist at recombinant GABA_A receptors^[1].
Ocinaplon inhibits [³H]flunitrazepam binding to native GABA_A receptors from rat cerebellar membranes with an IC₅₀ of 1.2 μM, which is 3-fold more potent than its inhibition of binding to rat cortical membranes (IC₅₀ 3.8 μM)^[2].
Ocinaplon (48 h) potentiates GABA-gated currents in 8 recombinant human GABA_A receptor isoforms expressed in Xenopus laevis oocytes, with the highest relative efficacy (85% of diazepam) and an EC₅₀ of 3.07 μM at the α1β2γ2S isoform, and lower efficacies at α2-, α3-, and α5-containing isoforms^[2]. In Vivo:Ocinaplon (3.1 mg/kg; p.o.; single dose; 1 hour pre-test) produces a Flumazenil (HY-B0009)-sensitive anxiolytic effect in the thirsty rat conflict test^[2].
Ocinaplon (9.6 mg/kg; p.o.; single dose; 1 hour pre-challenge) inhibits pentylenetetrazole-induced convulsions in rats with an oral ED₅₀ of 9.6 mg/kg^[2].
Ocinaplon (81.7-172.2 mg/kg; p.o.; single dose; 1 hour pre-test) impairs motor function in rats at oral ED₅₀ values of 81.7 mg/kg (motor activity), 172.2 mg/kg (inclined screen), and 92 mg/kg (rod walking), which are 5- to 10-fold higher than its anxiolytic dose^[2].
Ocinaplon (4-128 mg/kg; p.o.; single dose; 60 minutes pre-test) produces anxiolytic-like effects in squirrel monkeys at oral doses from 4 mg/kg to 64 mg/kg, with motor impairment-like effects only at the higher dose of 128 mg/kg^[2].