Talnetant

Modify Date: 2024-01-05 07:49:46

Talnetant structure	Common Name	Talnetant
	CAS Number	174636-32-9	Molecular Weight	382.45400
	Density	1.212g/cm3	Boiling Point	580.4ºC at 760mmHg
	Molecular Formula	C₂₅H₂₂N₂O₂	Melting Point	N/A
	MSDS	Chinese USA	Flash Point	304.8ºC
	Symbol	GHS06	Signal Word	Danger

Use of Talnetant

Talnetant (SB 223412) 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

Name	3-hydroxy-2-phenyl-N-(1-phenylpropyl)quinoline-4-carboxamide
Synonym	More Synonyms

Description	Talnetant (SB 223412) 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
Related Catalog	Signaling Pathways >> GPCR/G Protein >> Neurokinin Receptor Signaling Pathways >> Neuronal Signaling >> Neurokinin Receptor Research Areas >> Neurological Disease
References	[1]. Giardina GA, et al. Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 2. Identification of (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (SB 223412). J Med Chem. 1999 Mar 25;42(6):1053- [2]. Houghton LA, et al. Effect of the NK(3) receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans. Neurogastroenterol Motil. 2007 Sep;19(9):732-43. [3]. Dawson LA, 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 schizophrenia. Neuropsychopharmacology. 2008 Jun;33(7):1642-52.

Description

Related Catalog

Signaling Pathways >> GPCR/G Protein >> Neurokinin Receptor

Signaling Pathways >> Neuronal Signaling >> Neurokinin Receptor

Research Areas >> Neurological Disease

References

[1]. Giardina GA, et al. Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 2. Identification of (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (SB 223412). J Med Chem. 1999 Mar 25;42(6):1053-

[2]. Houghton LA, et al. Effect of the NK(3) receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans. Neurogastroenterol Motil. 2007 Sep;19(9):732-43.

[3]. Dawson LA, 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 schizophrenia. Neuropsychopharmacology. 2008 Jun;33(7):1642-52.

Density	1.212g/cm3
Boiling Point	580.4ºC at 760mmHg
Molecular Formula	C₂₅H₂₂N₂O₂
Molecular Weight	382.45400
Flash Point	304.8ºC
Exact Mass	382.16800
PSA	65.71000
LogP	6.06330
Vapour Pressure	4.51E-14mmHg at 25°C
Index of Refraction	1.657
Storage condition	2-8℃

Symbol	GHS06
Signal Word	Danger
Hazard Statements	H301
Precautionary Statements	P301 + P310
RIDADR	UN 2811 6.1 / PGIII

Precursor 5
CAS#:485-89-2 4-Quinolinecarb... CAS#:3789-59-1 ethylbenzylamine CAS#:4079-52-1 2-METHOXYACETOP... CAS#:41957-64-6 3-methoxy-2-phe...
CAS#:91-56-5 isatin
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