title: 2-Amino-6-chloro-3,4-dihydroquinazoline: A novel 5-HT3 receptor antagonist with antidepressant character.
abstract: 2-Amino-6-chloro-3,4-dihydroquinazoline HCl (A6CDQ, 4) binds at 5-HT3 serotonin receptors and displays antidepressant-like action in the mouse tail suspension test (TST). Empirically, 4 was demonstrated to be a 5-HT3 receptor antagonist (two-electrode voltage clamp recordings using frog oocytes; IC50=0.26μM), and one that should readily penetrate the blood-brain barrier (logP=1.86). 5-HT3 receptor antagonists represent a potential approach to the development of new antidepressants, and 4 is an example of a structurally novel 5-HT3 receptor antagonist that is active in a preclinical antidepressant model (i.e., the mouse TST).
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-540, USA. Electronic address: mdukat@vcu.edu.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Dukat
authors.forename: Katie
authors.initials: K
authors.lastname: Alix
authors.forename: Jessica
authors.initials: J
authors.lastname: Worsham
authors.forename: Shailesh
authors.initials: S
authors.lastname: Khatri
authors.forename: Marvin K
authors.initials: MK
authors.lastname: Schulte
mesh_terms: D000586:Amination; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry* / Q000494:pharmacology; D001001:Anura; D054879:Halogenation; D019417:Hindlimb Suspension; D051379:Mice; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D011799:Quinazolines; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists
keywords: 5-HT(3) receptors; Antagonists; Antidepressants; TST (tail suspension test)