From the Cover: Antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase.
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.
Kim
Sangwon F
SF
The Solomon H. Snyder Department of Neuroscience, Departments of Pharmacology and Molecular Sciences and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Huang
Alex S
AS
Snowman
Adele M
AM
Teuscher
Cory
C
Snyder
Solomon H
SH
D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D004789:Enzyme Activation / Q000187:drug effects; D007031:Hypothalamus / Q000201:enzymology*; D007150:Immunohistochemistry; D051379:Mice; D010766:Phosphorylation; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D011969:Receptors, Histamine H1; D000263:Adenylate Kinase