Research Reveals How Antipsychotic Drugs Cause Weight Gain

A histamine in many of these meds may be to blame, researchers say

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MONDAY, Feb. 12, 2007 (HealthDay News) -- Histamine may help spur the weight gain seen in patients taking certain kinds of antipsychotic drugs, researchers say.

In some cases, patients taking these drugs to treat mental illness gain so much weight that they develop serious complications such as heart disease and diabetes.

"We've now connected a whole class of antipsychotics to natural brain chemicals that trigger appetite. Our identification of the molecular players that link such drugs to increased food intake means there's now hope for finding a newer generation of drugs without the weight-gain side effects," Dr. Solomon H. Snyder, professor of neuroscienceat the Johns Hopkins School of Medicine in Baltimore, said in a prepared statement.

The Hopkins team suspected that certain antipsychotic drugs might trigger an overreaction in AMPK, an enzyme in brain cells that controls appetite in mice and likely does the same in humans.

To test this theory, the researchers injected mice with clozapine (Clozaril), a drug commonly prescribed to treat schizophrenia and bipolar disorders in people who respond poorly to conventional drugs.

AMPK activity quadrupled in the mice after they were given clozapine, the researchers report.

As their research progressed, the Hopkins team focused on a link between a histamine receptor, clozapine, AMPK activity and appetite. They injected clozapine into mice genetically engineered to lack the histamine receptor. The mice showed no increase in AMPK activity.

Histamine is already well known for its role in triggering allergy symptoms.

"Histamine also has a long history as a suspect in weight control, but no one ever could put a finger on the exact link," Snyder said. "The connection we've made between its receptor and appetite control is incredibly intriguing and opens new avenues for research on weight control, possibly including drugs that suppress appetite safely."

The study is expected to be published online in this week's issue of the Proceedings of the National Academy of Sciences.

More information

The American Academy of Family Physicians offers advice about weight control.

SOURCE: Johns Hopkins University, news release, Feb. 12, 2007

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