"目录号: HY-14552A
GPCR/G ProteinNeuronal Signaling-
Talnetant(SB 223412)盐酸盐是NK3受体选择性拮抗剂，在hNK-3-CHO细胞中Ki为1.4 nM，相对于hNK-2受体，Talnetant对于hNK-3有100倍的选择性，同时在100μM浓度下对hNK-1也无亲和力。
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生物活性
Description
Talnetant Hcl(SB 223412 Hcl) is a potent and selective NK3 receptor antagonist(ki=1.4 nM, hNK-3-CHO); 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 uM.IC50 Value: 1.4 nM (hNK-3-CHO binding Ki) [1]Target: NK3 receptorin vitro: In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits) [1]. Talnetant has high affinity for recombinant human NK3 receptors (pKi 8.7) and demonstrates selectivity over other neurokinin receptors (pKi NK2 = 6.6 and NK1<4). In native tissue-binding studies, talnetant displayed high affinity for the guinea pig NK3 receptor (pKi 8.5) [3].in vivo: Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days [2]. Talnetant (3-30 mg/kg i.p.) significantly attenuated senktide-induced 'wet dog shake' behaviors in the guinea pig in a dose-dependent manner. Microdialysis studies demonstrated that acute administration of talnetant (30 mg/kg i.p.) produced significant increases in extracellular dopamine and norepinephrine in the medial prefrontal cortex and attenuated haloperidol-induced increases in nucleus accumbens dopamine levels in the freely moving guinea pigs [3].Toxicity: Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo [2].Clinical trial: Study Of Talnetant Versus Placebo And Risperidone In Schizophrenia. Phase 2
Clinical Trial
GlaxoSmithKline
Irritable Colon
October 2004
Phase 2
GlaxoSmithKline
Schizophrenia
December 2004
Phase 2
GlaxoSmithKline
Schizophrenia
December 2004
Phase 2
GlaxoSmithKline
Schizophrenia
October 2002
Phase 2
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