174636-32-9

Talnetant is an antagonist of the neurokinin-3 (NK₃) receptor (K_i = 1 nM). 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.

Talnetant acts as a neurokinin 3 (NK3) receptor antagonist used as an antispychotic.

NK3

[1] H M SARAU. Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist.[J]. Journal of Pharmacology and Experimental Therapeutics, 1997, 281 3: 1303-1311.
[2] LEE A DAWSON. In Vitro and In Vivo Characterization of the Non-peptide NK3 Receptor Antagonist SB-223412 (Talnetant): Potential Therapeutic Utility in the Treatment of Schizophrenia[J]. Neuropsychopharmacology, 2007, 33 7: 1642-1652. DOI: 10.1038/sj.npp.1301549