Modafinil and modafinil analogues: free radical mechanism of the eugeroic and cognitive enhancment effect

Clifford W Fong (1)

1 Eigenenergy

Evidence is presented that strongly implicates the involvement of free radical species in the eugeroic and cognitive enhancement ability of modafinil and modafinil-like analogues via a dissociative electron transfer (DET) or attachment mechanism. Examination of modafinil and modafinil-like analogues which have been shown in the literature to exhibit wake promoting and cognitive psychobiological properties are shown in this study to produce free radicals when subject to electron attachment. Such observations are consistent with a free radical oxidative stress eugeroic and cognitive altering mechanism for modafinil and related analogues. It has also been shown that appropriate substitution of the acetamide moiety of modafinil can result in quite different DET behaviour, which holds promise of the ability to design and predict eugeroic and cognitive behaviour. In so far as DAT binding is a determinant of eugeroic and cognitive enhancing behaviour of modafinil-like analogues, a linear free energy relationship with DAT binding can also help identify the molecular properties of analogues which govern binding behaviour.

Mots clés: Modafinil; modafinil-like analogues; eugeroic effect; cognitive enhancement; free radicals; quantum mechanics

Domaines: Chimie thérapeutique; Chimie théorique et/ou physique

Clifford W Fong. Modafinil and modafinil analogues: free radical mechanism of the eugeroic and cognitive enhancment effect. [Research Report] Eigenenergy. 2018. ⟨hal-01933737⟩