Blonanserin extensively occupies rat dopamine D3 receptors at antipsychotic dose range

Antagonism of the dopamine D-3 receptor has been hypothesized to be beneficial for schizophrenia cognitive deficits, negative symptoms and extrapyramidal symptoms. However, recent animal and human studies have shown that most antipsychotics do not occupy D-3 receptors in vivo, despite their considerable binding affinity for this receptor in vitro. In the present study, we investigated the D-3 receptor binding of blonanserin, a dopamine D-2/D-3 and serotonin 5-HT2A receptors antagonist, in vitro and in vivo. Blonanserin showed the most potent binding affinity for human D-3 receptors among the tested atypical antipsychotics (risperidone, olanzapine and aripiprazole). Our GTP gamma S-binding assay demonstrated that blonanserin acts as a potent full antagonist for human D-3 receptors. All test-drugs exhibited antipsychotic-like efficacy in methamphetamine-induced hyperactivity in rats. Treatment with blonanserin at its effective dose blocked the binding of [3H]-(+)-PHNO, a D-2/D-3 receptor radiotracer, both in the D-2 receptor-rich region (striatum) and the D-3 receptor-rich region (cerebellum lobes 9 and 10). On the other hand, the occupancies of other test-drugs for D-3 receptors were relatively low. In conclusion, we have shown that blonanserin, but not other tested antipsychotics, extensively occupies D-3 receptors in vivo in rats. (C) 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.