Asenapine, a new sublingual atypical antipsychotic

Asenapine is an antagonist at various dopaminergic (D2, D3 and D4), serotonergic (5HT2A, 5HT2B, 5HT2C, 5HT6 and 5HT7) and alpha adrenergic receptors (α1A and α2). It has an appreciably high affinity for 5HT2A receptors than D2 receptors. The inhibition constant (Ki) ratio for 5HT2A/D2 receptors is approximately 20.[3] Antagonism of α2 adrenoceptors is said to improve the negative symptoms and cognitive function in schizophrenia. As asenapine blocks α2 receptors, it has the potential to offer these benefits. The antagonistic activity at α1 adrenoceptor accounts for the orthostatic hypotension caused by the drug.[4] Asenapine has no activity at muscarinic receptors in the therapeutic dose range. So asenapine does not cause any anticholinergic adverse effects and metabolic syndrome, which is seen with other atypical antipsychotics such as olanzapine and clozapine. It is also an antagonist at histamine H1 receptors and hence causes sedation. By its activity at H1 receptors, it was predicted to cause weight gain and has also done so in clinical trials.[4]