LY2794193

LY2794193 is a highly potent and selective mGlu3 receptor agonist (hmGlu3 K_i=0.927 nM，EC₅₀=0.47 nM; hmGlu2 K_i=412 nM，EC₅₀=47.5 nM)^[1]. In Vitro: LY2794193 exhihits inhibition of spontaneous Ca²⁺ oscillations in cultured rat cortical neurons with an EC₅₀ of 43.6 nM^[1].
In the rat cortical neuron Ca²⁺ oscillation assay, LY2794193 exhibits a biphasic inhibition of spontaneous Ca²⁺ transients (high affinity EC₅₀=0.44 nM; 48% of the total agonist response; low affinity EC₅₀=43.6 nM; 52% of the total agonist response) with combined maximal agonist efficacy (E_max) of 66%^[1]. In Vivo: LY2794193 (1-30 mg/kg, s.c.), given 30 min prior to PCP (5 mg/kg, s.c.) leads a dose-related reduction in ambulations^[1].
LY2794193 (1 mg/kg; i.v.) exhibits moderate clearance (18.3 mL/min per kg) and volume of distribution (1.17 L/kg) with a calculated plasma half-life (T_1/2) of 3.1 h in Male Sprague-Dawley rats^[1].
LY2794193 (3 mg/kg; s.c.) leads to the rapid appearance in the plasma (AUC=9.9 μM; C_max=6.78 μM; T_max=0.44 h) and a calculated bioavailability of 121% in male Sprague-Dawley rats^[1].