Increased food consumption by clozapine, but not by olanzapine, in satiated rats

Various drugs used to treat schizophrenia have been repeatedly shown to increase body weight in both animals and humans. There are different theories as to why this occurs, but the most recently studied theory is that these drugs which cause weight gain do so because of an antagonist effect at the 5HT2(c) receptor. In this work, we studied the effects of olanzapine, clozapine, and risperidone on feeding behavior. Over a 4-hour test period in satiated rats, clozapine, over a broad dose range, significantly increased food consumption. Similarly, risperidone increased food consumption relative to control. In contrast, olanzapine did not significantly increase food consumption in rats at any dose tested over the 4-hour test period. This suggests that olanzapine may be different from clozapine and risperidone with respect to potential weight gain in schizophrenic patients. Moreover, we believe that the effect produced by clozapine and risperidone is due to the alpha-adrenergic activity of these compounds, since olanzapine has a much lower affinity for alpha adrenergic receptors than does clozapine or risperidone, and not due to the 5HT2(c) activity, which all three compounds have in common. (C) 1997 Wiley-Liss, Inc.