Description
A nonpeptide NK3 antagonist (Ki = 1 nM); selective for NK3 over NK1 and NK2 receptors (Kis = 144 and >100,000 nM, respectively, in CHO cells expressing recombinant human receptors); inhibits neurokinin B-induced calcium mobilization in HEK293 cells expressing human NK3 receptors (IC50 = 16.6 nM); inhibits senktide-induced contractions in isolated rabbit iris sphincter muscle (pD2 = 9.1); reduces senktide-induced head shakes and tail whips in mice from 5-20 mg/kg; inhibits senktide-induced wet-dog shakes, increases extracellular dopamine and norepinephrine in the medial prefrontal cortex, and attenuates haloperidol-induced increases in nucleus accumbens dopamine levels in guinea pigs