We aim to computationally design, synthesise and pharmacologically test a number of guanidinium derivatives as alpha2-adrenoceptor antagonists with antidepressant application.Based on two recently discovered alpha2-AR antagonists, found in Rozas’ group, showing antidepressant activity, it is proposed to undertake a ligand based drug design strategy to identify pharmacophoric elements for antagonistic activity. In particular, the guanidinium cation is a very aprticular one that can establish not only ionic and hydrogen bond interactions but also cation-pi interactions with aromatic systems. All this type of interactions will eb also research.