Talnetant is an antagonist of the neurokinin-3 (NK3) receptor (Ki = 1 nM). It is selective for NK3 over NK1 and NK2 receptors (Kis = 144 and >100,000 nM, respectively, in CHO cells expressing recombinant human receptors). Talnetant inhibits calcium mobilization induced by neurokinin B in HEK293 cells expressing human NK3 receptors (IC50 = 16.6 nM). It inhibits contractions induced by the NK3 receptor agonist senktide in isolated rabbit iris sphincter muscle (pD2 = 9.1). Talnetant (5-20 mg/kg) reduces senktide-induced head shakes and tail whips in mice. It also 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.
