In what may be a major breakthrough for the research and development of antipsychotic drugs, brain scientists at Johns Hopkins University believe they have discovered a major cause of the weight gain suffered by many patients taking antipsychotic medication. Scientists now claim that powerful drugs such as Zyprexa (olanzapine), Clozaril (clozapine), and Risperdal (risperidone) may affect production of an enzyme known as AMPK, which influences appetite.
“We’ve now connected a whole class of antipsychotics to natural brain chemicals that trigger appetite,” said Dr. Solomon H. Snyder, professor of neuroscience at the Johns Hopkins School of Medicine. “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.”
The researchers tested their theory by injecting mice with clozapine, and they found that those mice “showed quadrupled AMPK activity.” A spike in AMPK production and activity leads to an increased appetite in mice, and researchers believe that AMPK has the same appetite-control function in humans. The authors of the study think that the increased AMPK activity caused by these drugs is a result of the effects the drugs have on the protein histamine and its receptor. The drugs may work to block the histamine receptor, which spurs AMPK activity.
“Histamine also has a long history as a suspect in weight control, but no one ever could put a finger on the exact link,” Dr. 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 findings are significant because of the increase in diabetes and heart disease associated with the weight gain caused by these types of drugs. The research, which was funded by the U.S. Public Health Service, Canadian Institute of Health Research, National Institutes of Health, and National Multiple Sclerosis Society, will be published in the Proceedings of the National Academy of Sciences later this month.
In related news, an FDA scientist, Dr. David Graham, testified today before Congress, claiming that the agency’s scrutiny and oversight of Zyprexa and similar antipsychotic drugs was lax and that the FDA is acutely aware of and concerned by the connection these medications have to weight gain, diabetes, and heart disease.