Acknowledgments The Oligomycin A price authors are grateful to Lindsey Stevens, Lynn Benham and the medicines management team at Southern Health NHS Foundation Trust for their support and assistance. Footnotes This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest related to this study.

The atypical antipsychotic drugs are considered a first-line Inhibitors,research,lifescience,medical treatment for mania in bipolar disorder with many having a proven superiority to the classical mood stabilisers. This review addresses

the pharmacological mechanisms underlying this therapeutic efficacy, as well as those mechanisms considered responsible for the adverse effects of antipsychotic drugs, with a particular focus on the recently

introduced asenapine. The high efficacy in bipolar mania of haloperidol, a relatively selective dopamine D2-like selleck chemical receptor antagonist, Inhibitors,research,lifescience,medical indicates that the one common receptor mechanism underlying antipsychotic effects on mania is antagonism at the D2 receptor. Serotonin receptors are implicated in antidepressant response, and relief of depressed mood in mixed Inhibitors,research,lifescience,medical states is likely to involve drug effects at one, or more likely several interacting, serotonin receptors. Asenapine shows a unique breadth of action at these sites, with potential effects at clinical doses at 5HT1A, 1B, 2A, 2C, 6 and 7 receptors. Antagonism Inhibitors,research,lifescience,medical at alpha2 adrenoceptors may also be involved. Adverse effects include those classically associated with dopamine D2 receptor blockade, the extrapyramidal side effects (EPS), and which are relatively diminished in the atypical (in comparison with the conventional) antipsychotics. A variety of protective mechanisms against EPS associated with different drugs include low D2 affinity, Inhibitors,research,lifescience,medical D2 partial agonism, high 5-HT2A and 2C antagonism. Similar effects

at the D2 and 5-HT2C receptors may underlie the low propensity for hyperprolactinaemia of the atypicals, although the strong prolactin-elevating Entinostat effect of risperidone reflects its relatively high blood/brain concentration ratio, a consequence of it being a substrate for the p-glycoprotein pump. Weight gain is a further concern of antipsychotic treatment of bipolar disorder which is particularly severe with olanzapine. Histamine H1, alpha1 adrenergic and particularly 5-HT2C receptors are implicated in this effect, although the lower propensity for weight gain shown by asenapine which, like olanzapine, binds to these receptors, indicates that other protective receptor mechanisms, or subtle differences in the 5-HT2C receptor-mediated effects, may be important. Of other peripheral and central effects, the pharmacological basis of sedation (H1 receptors) and postural hypotension (alpha1 adrenoceptors) are rather better understood.