M4 agonists/5HT7 antagonists with potential as antischizophrenic drugs: serominic compounds

C.J. Suckling, J.A. Murphy, A.I. Khalaf, S. Zhou, D.E. Lizos, A. Nguyen Van Nhien, H. Yasumatsu, A. McVie, L.C. Young, C. McCraw, P.G. Waterman, B.J. Morris, J.A. Pratt, A. Harvey

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Chronic low-dose treatment of rats with the psychomimetic drug, phencyclidine, induces regionally specific metabolic and neurochemical changes in the CNS that mirror those observed in the brains of schizophrenic patients. Recent evidence suggests that drugs targeting serotoninergic and muscarinic receptors, and in particular 5-HT7 antagonists and M4 agonists, exert beneficial effects in this model of schizophrenia. Compounds that display this combined pattern of activity we refer to as serominic compounds. Based upon leads from natural product screening, we have designed and synthesised such serominic compounds, which are principally arylamidine derivatives of tetrahydroisoquinolines, and shown that they have the required serominic profile in ligand binding assays and show potential antipsychotic activity in functional assays.
Original languageEnglish
Pages (from-to)2649-2655
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number9
DOIs
Publication statusPublished - 1 May 2007

Fingerprint

Tetrahydroisoquinolines
Phencyclidine
Muscarinic Receptors
Drug Delivery Systems
Biological Products
Antipsychotic Agents
Assays
Schizophrenia
Ligands
Brain
Pharmaceutical Preparations
Rats
Screening
Mirrors
Derivatives
Therapeutics

Keywords

  • anti-schizophrenic
  • M4 receptor agonist
  • 5HT7 receptor antagonist
  • tetrahydroisoquinolines
  • amidines

Cite this

Suckling, C.J. ; Murphy, J.A. ; Khalaf, A.I. ; Zhou, S. ; Lizos, D.E. ; Nguyen Van Nhien, A. ; Yasumatsu, H. ; McVie, A. ; Young, L.C. ; McCraw, C. ; Waterman, P.G. ; Morris, B.J. ; Pratt, J.A. ; Harvey, A. / M4 agonists/5HT7 antagonists with potential as antischizophrenic drugs: serominic compounds. In: Bioorganic and Medicinal Chemistry Letters. 2007 ; Vol. 17, No. 9. pp. 2649-2655.
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author = "C.J. Suckling and J.A. Murphy and A.I. Khalaf and S. Zhou and D.E. Lizos and {Nguyen Van Nhien}, A. and H. Yasumatsu and A. McVie and L.C. Young and C. McCraw and P.G. Waterman and B.J. Morris and J.A. Pratt and A. Harvey",
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Suckling, CJ, Murphy, JA, Khalaf, AI, Zhou, S, Lizos, DE, Nguyen Van Nhien, A, Yasumatsu, H, McVie, A, Young, LC, McCraw, C, Waterman, PG, Morris, BJ, Pratt, JA & Harvey, A 2007, 'M4 agonists/5HT7 antagonists with potential as antischizophrenic drugs: serominic compounds', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 9, pp. 2649-2655. https://doi.org/10.1016/j.bmcl.2007.01.093

M4 agonists/5HT7 antagonists with potential as antischizophrenic drugs: serominic compounds. / Suckling, C.J.; Murphy, J.A.; Khalaf, A.I.; Zhou, S.; Lizos, D.E.; Nguyen Van Nhien, A.; Yasumatsu, H.; McVie, A.; Young, L.C.; McCraw, C.; Waterman, P.G.; Morris, B.J.; Pratt, J.A.; Harvey, A.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 9, 01.05.2007, p. 2649-2655.

Research output: Contribution to journalArticle

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T1 - M4 agonists/5HT7 antagonists with potential as antischizophrenic drugs: serominic compounds

AU - Suckling, C.J.

AU - Murphy, J.A.

AU - Khalaf, A.I.

AU - Zhou, S.

AU - Lizos, D.E.

AU - Nguyen Van Nhien, A.

AU - Yasumatsu, H.

AU - McVie, A.

AU - Young, L.C.

AU - McCraw, C.

AU - Waterman, P.G.

AU - Morris, B.J.

AU - Pratt, J.A.

AU - Harvey, A.

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