Clozapine acts as an agonist at serotonin 2A receptors to counter MK-801-induced behaviors through a βarrestin2-independent activation of Akt.

ABSTRACT: The G protein-coupled serotonin 2A receptor (5-HT2AR) is a prominent target for atypical antipsychotic drugs, such as clozapine. Although clozapine is known to inhibit 5-HT2AR signaling through G protein-dependent mechanisms, it differs from classic GPCR antagonists, in that it also induces 5-HT2AR internalization and activates Akt signaling via a 5-HT2AR-mediated event. In this regard, clozapine may also be considered a functionally selective agonist. The cognate neurotransmitter at the 5-HT2AR, serotonin, also induces 5-HT2AR internalization and Akt phosphorylation. Serotonin promotes interactions with the scaffolding and regulatory protein, βarrestin2, which results in the recruitment and activation of Akt. These interactions prove to be critical for serotonin-induced, 5-HT2AR-mediated

SUBMITTER: Schmid CL 

PROVIDER: S-EPMC4059899 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature