Darigabat (PF-06372865, CVL-865) is a novel potent, α2/3 functionally selective GABAA receptor positive allosteric modulator with Ki of 2.9 nM, 21 nM, 134 nM for α2, α1 PAM, α2 PAM, respectively.
PF-06372865 (Darigabat) exhibits functional selectivity for receptors containing α2/3/5 subunits, with significant positive allosteric modulation (90-140%) but negligible activity (<20%) at GABAA receptors containing α1 subunits.
PF-06372865 (Darigabat) demonstrates a robust increase in saccadic peak velocity, increases in beta frequency qEEG and a slight saturating increase in body sway in clinical trials.
