However, there are some clear indications how certain receptor actions might be involved in both the beneficial and adverse SB216763 effects of these drugs, as well as some intriguing potential mechanisms as yet inadequately explored. Effects on bipolar symptoms The neuronal dysfunction that underlies mania and manic episodes remain obscure, even more so that the psychosis of schizophrenia. Inhibitors,research,lifescience,medical It is generally considered that the primary antipsychotic mechanism

in schizophrenia involves antagonist action at the dopamine D2 receptor; occupancy of this receptor in the striatum correlates best with relief of positive symptoms of the disease [Agid et al. 2007]. Given the similar efficacy of the atypical antipsychotic drugs in treating mania, an efficacy extending to the conventional antipsychotic haloperidol, which is especially effective Inhibitors,research,lifescience,medical [Tohen and Vieta, 2009; Cipriani et al. 2011], it seems likely that this mechanism

also underlies the anti-manic effect of all antipsychotic drugs. Mania is not inevitably psychosis, although it can develop psychotic features, and this suggests that the effects of the drugs are not solely ‘antipsychotic’ but are, using an outmoded description, ‘major tranquillizers’. Current hypotheses of antipsychotic action address the role of dopamine hyperfunction Inhibitors,research,lifescience,medical in the aberrant attribution of salience model of psychosis [Kapur, 2003]. Whether this salience dysregulation syndrome can extend to include mania is unclear [van Os, 2009]. However, of the other subjective effects of antipsychotic-induced dopamine blockade, a reduction in motivational drive [Henry et al. 2006; Mavrikaki et al. 2010] is one consequence Inhibitors,research,lifescience,medical that could result in attenuation of manic behaviour. Whatever the neuropsychological mechanism, the efficacy of the relatively selective high activity Inhibitors,research,lifescience,medical D2 antagonist haloperidol indicates that dopamine

D2 antagonism alone, or partial agonism/antagonism in the case of aripirazole, is a sufficient pharmacological mechanism for the relief of acute mania common to all antipsychotic drugs. The role, if any, of the D3 receptor Terminal deoxynucleotidyl transferase in these processes is as yet unclear, and we still have no clear understanding of the influence of the relatively higher affinities for this dopamine D2-like receptor subtype shown by asenapine and ziprasidone. What is likely to differentiate the antipsychotics in the treatment of bipolar disorder will therefore relate not solely to antimanic effects but also to other aspects of treatment relating to symptom relief and side effects. The other side of the bipolar disorder coin is depression. Of the atypicals, quetiapine is licensed for bipolar depression, while others including asenapine [Szegedi et al. 2011], have demonstrated the improvement of depressive symptoms in patients with manic episodes.