The affinities and functional activities of asenapine at neurotransmitter receptors have been systematically determined by Shahid et al. [2009]; the affinities from radioligand binding assays they reported will be discussed below. In common with all antipsychotic drugs asenapine has a high affinity for the dopamine D2 receptor, substantially higher, in fact, than the other atypical drugs other than the partial

agonist aripiprazole. Given that, as discussed below, it is the affinity at the dopamine Inhibitors,research,lifescience,medical D2 receptor that most likely mediates the anti-manic mechanism and thereby determines dose, affinity at other receptors can be described relative to the D2 value. Interestingly, asenapine has a higher affinity for the D3 subtype of the dopamine D2-like receptors

than for D2 itself, a property shared with ziprasidone alone among the atypicals. It also has a substantial affinity for the D4 receptor along with several, but not all, of the other atypicals, although there is now little to indicate this site is of functional Inhibitors,research,lifescience,medical importance in antipsychotic action. The high affinity of asenapine for the 5-HT2A receptor too is greater than that for the other atypicals, although all have effective antagonist activity at this site. It is the 5-HT2A Inhibitors,research,lifescience,medical activity that is the primary pharmacology considered to differentiate these atypical drugs from the conventional antipsychotics. Inhibitors,research,lifescience,medical What differentiates asenapine pharmacologically from the other atypical antipsychotics is the breadth of its activities at other 5-HT receptors. Thus antagonism at 5-HT2B, 5-HT2C, 5-HT5A, 5-HT6 and 5-HT7 receptors is apparent at affinities at or greater than that for the D2 receptor; activity at the 5-HT2C site is particularly high. Furthermore, activities at 5-HT1A and 5-HT1B receptors

may be great enough to have some functional effect at clinical doses. Asenapine appears to be a partial agonist at the 5-HT1A site [Ghanbari et al. 2009] as are most other check FAQ atypicals except Inhibitors,research,lifescience,medical for risperidone and olanzapine. Alpha1A adrenoceptor antagonism is likely to occur at clinical doses, an effect true for most other atypicals except aripiprazole. Asenapine has high relative affinities for the alpha2 adrenoceptors, as does clozapine and AV-951 quetiapine; risperidone too may have some activity, particularly at the alpha2C site. However, in functional assays, the activity of both risperidone and asenapine at these sites is relatively low [Shahid et al. 2009]. Three further receptor actions have been reported: asenapine is a relatively effective antagonist at histamine H1 receptors, as are quetiapine, olanzapine and clozapine, and is, uniquely, an antagonist at H2 receptors. It has no effect at the muscarinic receptors, in contrast to the relatively high affinities at these sites shown by clozapine and olanzapine.