Our previous studies on Alzheimer's disease patients revealed depression as a critical, difficult comorbidity. Also, the outcomes of extensive, preclinical and clinical pharmacological studies on procaine revealed its beneficial effects on depression, actually supported by new research insights reported in the international scientific literature. An extensive pharmacokinetic study of double labeled (99mTc/131Iodine) procaine in rats and a wide bibliographic study allowed us to decipher its detailed hydrolysis cascade. The correlation with pharmacodynamic data in rats and clinical investigations revealed new insights about procaine action mechanisms. We present a synopsis of its action mechanisms in depression, as well as our viewpoints related to the further improvement of this molecule. The new data argue the variegated and versatile actions on procaine, depending on the disbalance it encounters, due to the interplay of the metabolites issued along its Diethylaminoethanole and para-Aminobenzoic hydrolysis arms. It is able to restore the catechol/indolaminergic - cholinergic equilibrium, beneficially acting in both manic and depressive episodes. Especially a biochemical loop in the core of the hydrolysis picture polarizing inner feedback, feedbefore and feedsideward biochemical events seems responsible of procaine's interesting behavior. Its short-acting, selective, fully reversible and competitive monoamine oxidase and serotonin oxidative deamination inhibitions, interference with S-adenosylmethionine-homocysteine/folates cycles, methylome, gene expression and the cholinergic-dopaminergic reward link, among other, are commented. As argued by the most actual findings, far from being morally obsolete Procaine, like the 25-year-old Russian antihistamine Dimebon or deoxyazacytidine (Decitabine), requires and must be improved as a powerful gerontologic (preventive) and geriatric (curative) tool addressed to depression.