Abstract
Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT
1B/1D autoreceptors antagonists motivated us to incorporate SSRIs and 5HT
1B/1D antagonists in one ‘hybrid’ molecule. A library of virtual ‘hybrid’ molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (
K
i
=
0.013–5000
nM) and used as 3D query. Compounds with fit values (⩾2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action.