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NK3 receptor antagonists: the next generation of antipsychotics?

Abstract

Although current antipsychotic drugs are effective at treating the psychotic (positive) symptoms of schizophrenia, they have one or more serious side effects, including extrapyramidal symptoms, weight gain, cardiovascular liabilities and type II diabetes. However, recent data from clinical trials of selective neurokinin 3 (NK3) receptor antagonists in schizophrenia ? osanetant and talnetant ? have shown significant improvement in positive symptoms, with no major side-effects reported as yet. Here we discuss the preclinical and clinical evidence that indicates that NK3 receptor antagonists might represent a new approach to the treatment of schizophrenia and possibly other neuropsychiatric disorders.

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Figure 1: Tachykinin genes and peptides.
Figure 2: Neurokinin 3 receptor characteristics and expression.
Figure 3: Neurokinin 3 receptors and dopamine.
Figure 4: Effector systems of NK3 receptors.

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Acknowledgements

The authors gratefully thank T. Ballard-Yardy, P. David-Pierson, M.-C. Hernandez, T. Hoffmann, F. Knoflach, S. Nick, S. Poli, R. Porter, M. Schmitt, P. Schnider, L. Steward, A. Sleight, H. Stadler and J. Wettstein for discussions, ideas, commitments and support. We thank P. Shugrue for providing Fig 2Bb and X. Langlois for providing Fig 2Bc.

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Correspondence to Will Spooren.

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Competing interests

W.S. and C.R. are employees of F. Hoffmann-La Roche, which is developing drugs that target neurokinin receptors. H.M. is a consultant to Acadia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Pfizer, Solvay and Wyeth.

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DATABASES

Entrez Gene

D 2 receptor

5-HT 1A receptor

5-HT 2A receptor

5-HT 2C receptor

5-HT 6 receptor

5?HT 7 receptor

NK 1 receptor

NK 2 receptor

NK 3 receptor

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Spooren, W., Riemer, C. & Meltzer, H. NK3 receptor antagonists: the next generation of antipsychotics?. Nat Rev Drug Discov 4, 967–975 (2005). https://doi.org/10.1038/nrd1905

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