3H-Imipramine binding was measured in freshly prepared platelet membranes from 47 drug-free major depressives and 46 healthy controls. Where possible, platelet binding in depressed subjects was repeated following treatment. A significant negative correlation was found between Bmax and assay protein concentration and Bmax values were corrected for this effect. Adjusted Bmax was significantly lower (by 14%) in female depressed patients than in female control subjects, and the difference was of similar magnitude premenopausally and postmenopausally. No such difference was found in males. Kd did not differ significantly between depressed and control subjects. Multiple regression analysis confirmed significant effects on Bmax of presence of depressive illness, age (positive correlation), and season (higher in summer). Within the depressed sample, Bmax was significantly lower in those subjects with obsessional features. Endogenicity (Research Diagnostic Criteria or Newcastle), dexamethasone suppression test result, drug-free interval, family history of depression, depressive psychosis, suicidal ideation, and past history of suicide attempts were not significantly related to Bmax. Paired comparisons revealed no significant effect on Bmax of 6 weeks' treatment with imipramine, maprotiline, or BRL 14342 or of a course of electroconvulsive therapy.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/0165-1781(89)90189-3 | DOI Listing |
Eur J Pharmacol
October 2014
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla 3001, Querétaro 76230, México. Electronic address:
The pharmacological activity of bupropion was compared between α7 nicotinic acetylcholine receptors expressed in heterologous cells and hippocampal and dorsal raphe nucleus neurons. The inhibitory activity of bupropion was studied on GH3-α7 cells by Ca2+ influx, as well as on neurons from the dorsal raphe nucleus and interneurons from the stratum radiatum of the hippocampal CA1 region by using a whole-cell voltage-clamp technique. In addition, the interaction of bupropion with the α7 nicotinic acetylcholine receptor was determined by [3H]imipramine competition binding assays and molecular docking.
View Article and Find Full Text PDFPharmacol Res
October 2011
Clinical Brain Disorders Branch, GCAP, NIMH, NIH, Building 10, CRC 7-3342, 10 Center Dr., Bethesda, MD 20892, United States.
Early studies indicated that serotonin, a primary transmitter in the central nervous system, may not represent the primary endogenous regulator for the 5-HT2 receptor labeled by [3H]-ketanserin. Instead, an endogenous ligand may be responsible for modulating the [3H]-ketanserin site. Through different isolation and purification procedures, a pronase-sensitive peptide with activity on [3H]-ketanserin binding was identified in the rat brain.
View Article and Find Full Text PDFPharmacol Res
October 2011
Department of Neuroscience, University of Rome Tor Vergata, via Montpellier, 1-00133 Rome, Italy.
This article briefly outlines the background and major findings of the research projects in which, together with a number of skilled and enthusiastic collaborators, I was involved at FGIN under the mentorship of the late Dr. Erminio Costa.The topics covered are (ì) our search for an endogenous ligand of the [3H]-imipramine binding site, as an approach to shed light on the still today elusive mechanisms underlying the therapeutic action of antidepressant drugs; (ìì) our attempt to correlate psychopathological states, characterized by dysfunctions of the GABAergic neurotransmission, with an altered brain content of Diazepam binding inhibitor (DBI), a peptide that exerts a direct negative modulation of GABAA receptor function and also, by binding to the mitochondrial benzodiazepine receptor, increases the brain content of GABAA receptor-active neurosteroids; (ììì) our demonstration that the activation of the glutamate/NMDA receptor, throughstimulation of several intracellular signaling pathways, induces the expression of the early inducible gene c-fos, a mechanism proposed to underlie glutamate-mediated neuronal plasticity.
View Article and Find Full Text PDFBiochim Biophys Acta
December 2008
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Radioligand binding, photoaffinity labeling, and docking and molecular dynamics were used to characterize the tricyclic antidepressant (TCA) binding sites in the nicotinic acetylcholine receptor (nAChR). Competition experiments indicate that the noncompetitive antagonist phencyclidine (PCP) inhibits [3H]imipramine binding to resting (closed) and desensitized nAChRs. [3H]2-azidoimipramine photoincorporates into each subunit from the desensitized nAChR with approximately 25% of the labeling specifically inhibited by TCP (a PCP analog), whereas no TCP-inhibitable labeling was observed in the resting (closed) state.
View Article and Find Full Text PDFJ Pharmacol Toxicol Methods
June 2006
Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada and Co., 16711 Trans Canada Hwy., Kirkland, Quebec, Canada H9H 3L1.
Introduction: Covalent protein binding of metabolically reactive intermediates of drugs has been implicated in drug toxicity including the occurrence of idiosyncratic drug toxicity. Investigators therefore would prefer to avoid developing compounds that produce significant amounts of reactive metabolites. By incubating the radiolabeled drug of interest with liver microsomes it is possible to evaluate the propensity of a drug candidate to covalently bind to proteins.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!