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Neuropsychopharmacology (2003) 28, 519526

Gain for Typical and Atypical Antipsychotic Drugs[notdef]

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[notdef]Wesley K Kroeze*,1,2, Sandra J Hufeisen2, Beth A Popadak2, Sean M Renock2, SeAnna Steinberg2, Paul

Ernsberger3,4, Karu Jayathilake5,6, Herbert Y Meltzer5,6 and Bryan L Roth1,2,7,81Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH, USA; 2NIMH Psychoactive Drug ScreeningProgram, Case Western Reserve University Medical School, Cleveland, OH, USA;3Department of Nutrition, Case Western Reserve UniversityMedical School, Cleveland, OH, USA;4Department of Pharmacology, Case Western Reserve University Medical School, Cleveland, OH, USA;5Department of Psychiatry, Vanderbilt University Medical School, Nashville, TN, USA; 6Department of Pharmacology, Vanderbilt UniversityMedical School, Nashville, TN, USA;7Department of Psychiatry, Case Western Reserve University, Medical School, Cleveland, OH, USA;8Department of Neurosciences, Case Western Reserve University, Medical School, Cleveland, OH, USAAs a result of superior efficacy and overall tolerability, atypical antipsychotic drugs have become the treatment of choice for schizophreniaand related disorders, despite their side effects. Weight gain is a common and potentially serious complication of some antipsychotic drugtherapy, and may be accompanied by hyperlipidemia, hypertension and hyperglycemia and, in some extreme cases, diabetic ketoacidosis.The molecular mechanism(s) responsible for antipsychotic drug-induced weight gain are unknown, but have been hypothesized to bebecause of interactions of antipsychotic drugs with several neurotransmitter receptors, including 5-HT2A and 5-HT2C serotonin

receptors, H1-histamine receptors, a1- and a2-adrenergic receptors, and m3-muscarinic receptors. To determine the receptor(s) likely to

be responsible for antipsychotic-drug-induced weight gain, we screened 17 typical and atypical antipsychotic drugs for binding to 12neurotransmitter receptors. H1-histamine receptor affinities for this group of typical and atypical antipsychotic drugs were significantly

correlated with weight gain (Spearman r 0.72; po0.01), as were affinities for a1A adrenergic (r 0.54; po0.05), 5-HT2C

(r 0.49; po0.05) and 5-HT6 receptors (r 0.54; po0.05), whereas eight other receptors affinities were not. A principal

components analysis showed...

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H1-Histamine Receptor Affinity Predicts Short-Term Weight Gain for Typical and Atypical Antipsychotic Drugs

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H1-Histamine Receptor Affinity Predicts Short-Term Weight Gain for Typical and Atypical Antipsychotic Drugs

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