Atypical antipsychotics (AATPs) are currently used to treat a variety of psychiatric conditions, however most AATPs have been linked to metabolic side effects such as excessive weight gain.
Over a six-week period, researchers found that treatment with olanzapine acutely increased food intake, impaired glucose tolerance and altered physical activity and energy expenditure in C57BL/6 mice. The drug also had a sedative effective, which is thought to contribute to weight gain in humans.
To explore olanzapine’s mode of action the researchers examined its effect on mice lacking the serotonin 2C receptor (HTR2C). They found that the drug’s effect on weight gain was significantly blunted and glucose tolerance was not significantly altered either. Although its effect on physical activity and energy expenditure persisted.
These findings support the idea that olanzapine acts on multiple receptors but suggest that HTR2C agonists may be useful in preventing some of the associated metabolic side effects, the researchers concluded in The Journal of Clinical Investigation (online, 14 August 2017)
 Lord C, Wyler S, Wan R et al. The atypical antipsychotic olanzapine causes weight gain by targeting serotonin receptor 2C. J Clin Invest 2017. doi: 10.1172/JCI93362