Abstract. Antipsychotic drugs induce weight gain and metabolic abnormalities. Recently, the role of adipocytokines secreted from adipocytes in the development of metabolic syndrome has received attention. The aim of this study was to investigate the effects of chlorpromazine (Cp) on body weight, glucose, lipid metabolism, and adipocytokine secretion in rats fed sucrose. Wistar rats received 15% sucrose (Suc group), 15% sucrose and Cp at 7.5 mg / kg per day (Suc + Cp group), or Cp alone (Cp group) in water for 10 weeks. Fasting glucose levels in the Suc and Suc + Cp groups were significantly higher than in the control (Cont) group. Fasting insulin levels in the Suc, Suc + Cp, and Cp groups were also significantly higher than in the Cont group. The adiponectin level in the Suc group was significantly higher than in the Cont group, although the adiponectin level in the Suc + Cp group was not. Furthermore, the plasma tumor necrosis factor (TNF)-α level in the Suc + Cp group was significantly higher than in the Suc group. These data suggest that Cp inhibits the compensatory response of adiponectin with respect to obesity due to increased expression of plasma TNF-α level. Cp may exert more harmful effects on the glucose level and insulin resistance than on other factors, which may be one of the mechanisms responsible for the metabolic syndrome induced by antipsychotic agents.

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Purpose There are individual differences in the effects of antipsychotic drugs. As the genetic polymorphisms of several reseptors are thought to be a cause of individual differences, we investigated the effects of the genetic polymorphisms in serotonin receptors, histamine receptor and serotonin transporter genes on the clinical outcome of olanzapine. Methods: Patients of schizophrenia were enrolled simultaneously at St. Marianna University hospital with their written informed consent. In this study was approved by the institutional review board at St. Marianna University School of Medicine. Patients were given olanzapine (5~20mg) and blood were collected at 8weeks after drug administration. Clinical symptoms were evaluated by the PANSS scores before drug administration and at 4~8weeks of follow up. Genomic DNA were extracted from peripheral blood samples to analyze genetic polymorphisms 5HT2A (25Thr/Asp, 102T/C, 452His/Tyr, ‐1438G/A), 5HT2C (23Cys/Ser), 5HTTLPR (‐1396 44bp Ins/Del), H2R (‐1018G/A), by PCR‐RFLP and the method of direct sequence. Results: The polymorphic groups of 5HT2A (452His/Tyr, ‐1438G/A) and 5HT2C (23Cys/Ser) were prone to present better PANSS scores compared to the wild type group, whereas the group of 5HT2A(102T/C) showed insignificant results. It is necessary to analyze more number of cases. Clinical Pharmacology & Therapeutics (2004) 75, P18–P18; doi: