title: M4 agonists/5HT7 antagonists with potential as antischizophrenic drugs: serominic compounds.
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-HT(7) antagonists and M(4) 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.
authors.affiliation: Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland, UK. c.j.suckling@strath.ac.uk
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Suckling
authors.forename: John A
authors.initials: JA
authors.lastname: Murphy
authors.forename: Abedawn I
authors.initials: AI
authors.lastname: Khalaf
authors.forename: Sheng-ze
authors.initials: SZ
authors.lastname: Zhou
authors.forename: Dimitris E
authors.initials: DE
authors.lastname: Lizos
authors.forename: Albert Nguyen
authors.initials: AN
authors.lastname: van Nhien
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yasumatsu
authors.forename: Allan
authors.initials: A
authors.lastname: McVie
authors.forename: Louise C
authors.initials: LC
authors.lastname: Young
authors.forename: Corinna
authors.initials: C
authors.lastname: McCraw
authors.forename: Peter G
authors.initials: PG
authors.lastname: Waterman
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morris
authors.forename: Judith A
authors.initials: JA
authors.lastname: Pratt
authors.forename: Alan L
authors.initials: AL
authors.lastname: Harvey
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007700:Kinetics; D008968:Molecular Conformation; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043588:Receptor, Muscarinic M4 / Q000737:chemistry*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D018721:Muscarinic Agonists; D043588:Receptor, Muscarinic M4; D001285:Atropine; D000661:Amphetamine