Tesofensine (0.5-3.0 mg/kg, s.c.) induced a dose-dependent and marked decline in food intake with an ED50 of 1.3 mg/kg. The hypophagic

response of tesofensine (1.5 mg/kg, s.c.) was almost completely reversed by co-administration of prazosin (1.0 mg/kg, alpha(1) adrenoceptor antagonist) and partially antagonized by co-administration of SCH23390 (0.03 mg/kg, DA D-1 receptor antagonist). In contrast, tesofensine-induced hypophagia was not affected by RX821002 (0.3 mg/kg, alpha(2) adrenoceptor antagonist), haloperidol (0.03 mg/kg, D-2 receptor antagonist), NGB2904 (0.1 mg/kg, D-3 receptor antagonist), or ritanserin (0.03 mg/kg, 5-HT2A/C receptor antagonist). Hence, the mechanism underlying the suppression of feeding by tesofensine in the obese rat is dependent on the drug’s ability to indirectly stimulate alpha(1) Epacadostat cost adrenoceptor and DA D-1 CRT0066101 chemical structure receptor function. Neuropsychopharmacology ( 2010) 35, 1464-1476; doi: 10.1038/npp.2010.16; published online 3 March 2010″
“Recent studies have implicated alterations in the expression of polyamine-related genes in the brains of suicide completers including widespread downregulation

of spermidine/spermine N1-acetyltransferase, the key enzyme in polyamine catabolism, suggesting compensatory mechanisms attempting to increase brain levels of polyamines. Given the complexity of the polyamine system, quantification of the levels of the polyamines is an essential step in understanding the downstream effects of dysregulated gene expression. We developed a method using high-resolution capillary gas chromatography ( GC) in combination with mass spectrometry ( MS) for quantitation of polyamines from post-mortem brain tissue, which allowed us to accurately measure spermidine and putrescine concentrations in post-mortem brain tissues. Using this method, we analyzed putrescine and spermidine levels in a total of 126 samples from Brodmann areas 4, 8/9, and 11, from 42 subjects, comprising 16 suicide completers with major depression, 13 non-depressed suicide completers,

and 13 control subjects. Both putrescine and spermidine levels fell within the expected nanomolar ranges and were significantly elevated in the brain of suicide completers with a history of major depression as compared with controls. These Alectinib mouse results were not accounted by possible confounders. This is the first GC-MS study to analyze the expression of putrescine and spermidine from post-mortem brain tissue and confirms the hypothesis raised by previous studies indicating alterations in putrescine and spermidine levels in suicide/major depression. Neuropsychopharmacology ( 2010) 35, 1477-1484; doi: 10.1038/npp.2010.17; published online 3 March 2010″
“Changes in the brain’s cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer’s disease, schizophrenia, and depression.