Insight from "Calcium Paradox" due to Ca2+/cAMP Interaction: Novel Pharmacological Strategies for the Treatment of Depression

Abstract

Our discovery of “calcium paradox” phenomenon due to interaction of Ca2+/cAMP intracellular signalling pathways (Ca2+/cAMP interaction) may provide new insights for the treatment of psychiatric disorders, such as depression. This disorder is mainly resulting by reduction of serotonin and catecholamine release in central nervous system. Since 1975, several clinical studies have reported that administration of L-type Ca2+ channel blockers (CCBs) produces reduction in vascular resistance and arterial pressure in hypertensive patients, associated with an increase in plasma noradrenaline levels and tachycardia characterized by sympathetic hyperactivity. During almost four decades, these enigmatic phenomena remained unclear. In 2013, we discovered that this paradoxical sympathetic hyperactivity produced by CCBs is mediated by Ca2+/cAMP interaction. Then, the pharmacological manipulation of this interaction could be a more efficient therapeutic strategy for increasing serotoninergic and monoaminergic neurotransmission in depression.