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Atypical Antipsychotics Block Histamine, Increase Appetite

Drugs block histamine, activate AMP kinase, and may cause weight gain

WEDNESDAY, Feb. 21 (HealthDay News) -- Newer atypical antipsychotic medications, such as olanzapine and clozapine, may be causing unwanted weight-gain side effects because they block histamine receptors in the brain, according to a report published online Feb. 20 in the Proceedings of the National Academy of Sciences Early Edition.

Solomon Snyder, M.D., of the Johns Hopkins University School of Medicine in Baltimore, and colleagues examined how these atypical antipsychotic medications affect the activity of the enzyme AMP kinase (AMPK) in the hypothalamus, the brain region that regulates food intake.

The investigators found that both medications increased the activity of AMPK as detected by immunohistochemistry on hypothalamic brain slices. In addition, clozapine could reverse the effects of the anorexigenic peptide leptin on AMPK activity. The atypical antipsychotics were found to activate AMPK by blocking the histamine H1 receptor, an action similar to other antihistamine drugs.

"These findings may afford a means of developing more effective therapeutic agents and provide insight into the hypothalamic regulation of food intake," the authors write.

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