SSD114

SSD114 is a novel GABA_B receptor positive allosteric modulator. IC50 & Target: GABA_B receptor^[1] In Vitro: In the presence of 10 µM GABA, SSD114 at 25 µM significantly increases (to approximately 170% above basal levels) the [³⁵S]GTPγS stimulation induced by GABA alone. SSD114, added at 15 and 30 µM, induces a leftward shift of the GABA concentration-response curve with a slight concomitant increase of maximal GABA stimulation at the highest concentration. In the presence of both 15 and 30 µM SSD114, the EC₅₀ for GABA decreases by 2 and 2.5 fold, respectively, while the maximal stimulation (Emax) is potentiated only at the concentration of 30 µM, reaching 161±5.09% over the basal value^[1] . In Vivo: The onset of loss of righting reflex (LORR) is reduced by pretreatment with SSD114 [F_(5,30)=4.55, P<0.005]. Post hoc analysis indicates that the onset of LORR is significantly lower in mouse groups pretreated with doses of SSD114 equal to or higher than 10 mg/kg than in vehicle-treated mice. The duration of LORR is increased by pretreatment with SSD114 [F_(5,30)=4.81, P<0.005]. Post hocanalysis indicates that the duration of LORR is significantly longer in mouse groups pretreated with 10 and 100 mg/kg SSD114 than in vehicle-treated mice. A tendency toward a significant reduction (P=0.059) is observed in the mouse group pretreated with 30 mg/kg SSD114^[1].