5-HT2A deletion protects against Clozapine-induced hyperglycemia.

ABSTRACT

Clozapine is an antipsychotic known for its superior efficacy in treating drug-resistant Schizophrenia. However, Clozapine induces various side effects such as hyperglycemia, agranulocytosis, weight gain etc. The mechanisms of these Clozapine-induced side effects have remained largely elusive though an important role is ascribed to 5-HT2A (Serotonin receptor subtype-2A). In this pilot study, we report for the first time that the 5-HT2A 'global' knockout mice (Htr2a-/-) are resistant to the Clozapine-induced hyperglycemia. Importantly though, the Htr2a-/- mice exhibit near normal basal glucose metabolism in the glucose tolerance tests. Collectively, the Htr2a-/- mice provide an important tool to study the Clozapine-induced hyperglycemia.