Talnetant hydrochloride

Talnetant is an antagonist of the neurokinin-3 (NK₃) receptor (K_i = 1 nM).¹ It is selective for NK₃ over NK₁ and NK₂ 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 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.²

1.Sarau, H.M., Griswold, D.E., Potts, W., et al.Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonistJ. Pharmacol. Exp. Ther.281(3)1303-1311(1997) 2.Dawson, L.A., Cato, K.J., Scott, C., et al.In vitro and in vivo characterization of the non-peptide NK3 receptor antagonist SB-223412 (talnetant): Potential therapeutic utility in the treatment of schizophreniaNeuropsychopharmacology33(7)1642-1652(2008)