PM426. Effect of a glucagon-like peptide 1 (GLP-1) receptor agonist, liraglutide, on cognition and body weight during antipsychotic treatment

Objective: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, whereas it occurs fatal hematopoietic toxicity as agranulocytosis. To elucidate mechanism of hematopoietic toxicity by clozapine, we tried to develop the in vitro assay systems using HL-60 cells, and investigated the effect on hematopoiesis. Method: HL-60 cells were differentiated by all-trans retinoic acid (ATRA) to three states according hematopoietic process: undifferentiated HL-60 cells, under granulocytic ATRA-differentiation and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. Result: In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, clozapine (50 and 100 M) and doxorubicin, but not olanzapine decreased survival rate. Under granulocytic differentiation for 5 days, clozapine, even at 25 M, decreased survival rate without affecting granulocytic differentiation, increased caspase activity, and resulted in induction of apoptosis rather than necrosis. Lower concentrations of clozapine (