Antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase
Proceedings of the National Academy of Sciences, 2007•National Acad Sciences
The atypical antipsychotic drugs (AAPDs) have markedly enhanced the treatment of
schizophrenias but their use has been hindered by the major weight gain elicited by some
AAPDs. We report that orexigenic AAPDs potently and selectively activate hypothalamic
AMP-kinase, an action abolished in mice with deletion of histamine H1 receptors. These
findings may afford a means of developing more effective therapeutic agents and provide
insight into the hypothalamic regulation of food intake.
schizophrenias but their use has been hindered by the major weight gain elicited by some
AAPDs. We report that orexigenic AAPDs potently and selectively activate hypothalamic
AMP-kinase, an action abolished in mice with deletion of histamine H1 receptors. These
findings may afford a means of developing more effective therapeutic agents and provide
insight into the hypothalamic regulation of food intake.
The atypical antipsychotic drugs (AAPDs) have markedly enhanced the treatment of schizophrenias but their use has been hindered by the major weight gain elicited by some AAPDs. We report that orexigenic AAPDs potently and selectively activate hypothalamic AMP-kinase, an action abolished in mice with deletion of histamine H1 receptors. These findings may afford a means of developing more effective therapeutic agents and provide insight into the hypothalamic regulation of food intake.
National Acad Sciences