Abstract
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 D1 and D2 receptor stimulation increases intracellular sodium concentrations. D1 and D2 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.