Atypical antipsychotic properties of blonanserin, a novel dopamine D2 and 5-HT2A antagonist

Blonanserin is a novel antipsychotic agent that preferentially interacts with dopamine D2 and 5-HT2A receptors. To assess the atypical properties of blonanserin, we evaluated its propensity to induce extrapyramidal side effects (EPS) and to enhance forebrain Fos expression in mice. The actions of AD-6048, a primary metabolite of blonanserin, in modulating haloperidol-induced EPS were also examined. Blonanserin (0.3–10 mg/kg, p.o.) did not significantly alter the pole-descending behavior of mice in the pole test or increase the catalepsy time, while haloperidol (0.3–3 mg/kg, p.o.) caused pronounced bradykinesia and catalepsy. Blonanserin and haloperidol at the above doses significantly enhanced Fos expression in the shell (AcS) region of the nucleus accumbens and dorsolateral striatum (dlST). The extent of blonanserin-induced Fos expression in the AcS was comparable to that induced by haloperidol. However, the striatal Fos expression by blonanserin was less prominent as compared to haloperidol. Furthermore, combined treatment of AD-6048 (0.1–3 mg/kg, s.c.) with haloperidol (0.5 mg/kg, i.p.) significantly attenuated haloperidol-induced bradykinesia and catalepsy. The present results show that blonanserin behaves as an atypical antipsychotic both in inducing EPS and enhancing forebrain Fos expression. In addition, AD-6048 seems to contribute at least partly to the atypical properties of blonanserin.