Antipsychotic drugs have alleviated the debilitating symptoms of thousands of patients with schizophrenia and bipolar disorder, but often at a high price. These drugs can also trigger excessive weight gain, leading to life-threatening complications such as diabetes or heart disease. Now scientists at Johns Hopkins University have uncovered the mechanism by which these drugs stimulate the appetite—a finding that could lead to new agents without the side effect of constant hunger.
Neuroscientists Solomon H. Snyder and Sangwon Kim found that when they administered clozapine, a powerful antipsychotic, to mice, the animals experienced a spike of the appetite-stimulating enzyme AMPK. Then they discovered that blocking a receptor for histamine caused a boost in AMPK similar to the effects of clozapine. Histamine, well known for causing allergy symptoms, has been long suspected to play a role in weight control, but the mechanism has been unknown. The researchers confirmed their finding by administering clozapine to mice genetically engineered to lack the histamine receptor, and these rodents showed no increase in AMPK.