Effect of dopamine on intracellular sodium: A common pathway for pharmacological mechanism of action in bipolar illness

Background. The pathogenesis of bipolar illness is unknown. A search for common mechanism of action in effective medications has been utilized as a method to gain clues into mechanisms of illness. The recent increase of reports of documented efficacy of first-and second-generation antipsychotics in the control of mania offers a new opportunity to gain insight into the pathophysiological mechanism of bipolar disorder. Methods. A selected critical review of the literature is performed to gain insights into the effect of antipsychotic medications on ion regulation. Results. Dopamine D-1 and D-2 receptor stimulation increases intracellular sodium concentrations. D-1 and D-2 blockade normalizes stimulated intracellular sodium concentrations, and increases active sodium pump expression. Conclusions. A similar exercise has previously suggested that lithium and effective anticonvulsants reduce sodium influx in an activity-dependent manner. The current review suggests that antipsychotic medications may have a similar effect by a different mechanism. The role of ion dysregulation in the genesis of mania in bipolar illness needs to continue to be examined.