Weight gain can be a serious problem for patients taking antipsychotic drugs for schizophrenia - not only drugs have a sedative effect that slows people down, but they also stimulate the appetite, a combination that can mean a significant weight gain. It turns out that this is also what some antihistamines, which counteract allergic reactions are. Now, scientists say they have identified a common mechanism: the two types of drugs act on the same histamine receptor in the brain. Knowledge should help drug manufacturers to avoid this side effect in the next generation of antipsychotic drugs and other drugs.
Previous research had already suggested that the actions of a particular enzyme, AMP kinase (AMPK), are directly related to appetite control, apparently by an action on the H1 histamine receptor. To see if antipsychotic drugs cause excessive production of the enzyme, researchers led by neuroscientist Solomon Snyder of Johns Hopkins University in Baltimore, Maryland, injected mice with clozapine, an antipsychotic medication commonly prescribed. The injection resulted in quadrupled AMPK activity in the brains of mice. The researchers then gave the mice leptin, an appetite suppressant hormone, and saw the AMPK levels down.
The scientists then established the link of histamine giving elevated clozapine to mice lacking H1 receptor. In this case, the mouse does not react with high levels of AMPK, showing that stimulation of the enzyme by the drug depends on the stimulation of the H1 histamine receptor, researchers report online this week in the Proceedings of the National Academy of sciences . "We have now connected a whole class of antipsychotics to natural brain chemicals that trigger appetite," said Snyder.
The first antipsychotic, chlorpromazine, was originally designed as an antihistamine when was invented in the early 1950s, neuropsychopharmacologist Bryan Roth notes the University of North Carolina, Chapel Hill. Roth previous research has shown that many antipsychotics, besides targeting neurotransmitters linked to schizophrenia appears to activate signaling pathway mediated by H1 receptors But now, he said, the mechanism has been permanently nailed he said.. "I think this will go a long way toward convincing pharmaceutical companies and regulators that medication taken by humans we need to avoid hitting the receiver to avoid weight gain. "
Related Sites
- Information on atypical antipsychotics
- About histamine
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