2-Amino-6-chloro-3,4-dihydroquinazoline: A novel 5-HT3 receptor antagonist with antidepressant character

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 = 0.26 μM), and one that should readily penetrate the blood–brain barrier (log P = 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).