A novel potential therapeutic avenue for autism: design, synthesis and pharmacophore generation of SSRIs with dual action.

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Ghoneim OM, Ibrahim DA, El-Deeb IM, Lee SH, Booth RG

A novel potential therapeutic avenue for autism: design, synthesis and pharmacophore generation of SSRIs with dual action.

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6714-23. doi: 10.1016/j.bmcl.2011.09.046. Epub 2011 Sep 21.

PubMed ID

21982496 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Ergotamine	5-hydroxytryptamine receptor 1B	Ki (nM)	2.1	N/A	N/A	Details
Ergotamine	5-hydroxytryptamine receptor 1D	Ki (nM)	4.3	N/A	N/A	Details