Description
Talnetant is an antagonist of the neurokinin-3 (NK
3) receptor (K
i = 1 nM). It is selective for NK
3 over NK
1 and NK
2 receptors (K
is = 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 NK
3 receptors (IC
50 = 16.6 nM). It inhibits contractions induced by the NK
3 receptor agonist senktide in isolated rabbit iris sphincter muscle (pD
2 = 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.
