Local researchers said they have found why taking risperidone, an atypical antipsychotic drug, leads to weight gain.
The study was the first to identify the cause of weight gain at the level of nerve cells and molecules, they said. In the past, doing so was impossible because obesity found in patients could not be reproduced in animal models.
On Monday, the Korea Advanced Institute of Science and Technology (KAIST) said the joint research team of Professor Sohn Jong-woo of the Department of Biological Sciences at KAIST and Professor Chen Liu at the Department of Neuroscience of The University of Texas Southwestern Medical Center, Dallas, TX, discovered the cause of obesity that occurs after taking risperidone.
Atypical antipsychotics block brain neurotransmitters by binding to dopamine receptors and serotonin receptors in the central nervous system. They are called atypical because they have multiple pharmacological actions.
Atypical antipsychotic drugs are used for various neuropsychiatric disorders such as schizophrenia, bipolar disorder, and autism spectrum disorder. Compared to typical antipsychotic drugs, they cause fewer movement disorders but induce excessive appetite and obesity.
The researchers fed mice with risperidone-containing food and reproduced drug-induced appetite and obesity in mice. Using the animal models, the researchers found that risperidone reduces reactivity to melanocortin, one of the important neurotransmitters that suppress appetite, in the hypothalamus, a brain region that controls homeostasis.
The researchers also found how to prevent obesity while maintaining the effect of the atypical antipsychotic drug. Taking setmelanotide, an appetite suppressant that increases the activity of melanocortin-responsive nerve cells, could do the work, they said.
Feeding setmelanotide with risperidone in schizophrenia-modeled mice showed that risperidone’s antipsychotic effect was preserved while preventing obesity, the researchers confirmed.
Setmelanotide, approved by the FDA in November last year with the brand name Imcivree, is prescribed to treat obesity caused by several genetic factors.
“The study was the first to discover the cause of appetite increase and obesity induced by atypical antipsychotic drugs at the level of nerve cells and molecules. This will help treat neuropsychiatric diseases using these drugs,” Sohn said.
Although the research team confirmed that risperidone lowered the reactivity of melanocortin in the hypothalamus, they have not found whether this phenomenon could be applied to other atypical antipsychotic drugs, he said, adding he will focus research on figuring this out.
The study, titled “The Atypical Antipsychotic Risperidone Targets Hypothalamic Melanocortin 4 Receptors to Cause Weight Gain,” was published in the Journal of Experimental Medicine on Wednesday. The National Research Foundation of Korea sponsored the study through a senior researcher-supporting program.