Abstract：
:The dopamine (D2) receptor blocking property of antipsychotic medications has been proposed as the mechanism of the therapeutic activity of this class of drugs. This property has also been exploited as a method to quantify therapeutic levels of these drugs in patients. However, the lack of correlation among dosage, blood levels and clinical response has resulted in a contradictory literature on both mechanism and quantification of these drugs. Bioactivity and chemical identity of the commonly prescribed neuroleptic drug fluphenazine and its metabolites in human plasma were determined by a new method which combines the selectivity of chemical methods with the sensitivity and bioassay of the radioreceptor assay (RRA) method. Fluphenazine and its metabolites were separated and identified in human plasma by an ion-pairing reverse phase high performance liquid chromatographic method with electrochemical detection. A volatile buffer system was employed which was compatible with facile sample preparation for post-column analyses, and which provided sharp, symmetrical chromatographic peaks of parent compound and metabolites. Post chromatography, HPLC fractions were assayed by RRA for D2, alpha 1 and sigma receptors. More than one pattern of metabolism of the drug was seen, including biosynthesis of drug metabolites with biological activities at these receptor types. The individual differences with which this occurs may contribute to the variabilities seen in clinical response to neuroleptics, and to difficulties in neuroleptic blood level determinations.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Hoffman DW,Shillcutt SD,Edkins RDdoi
10.1016/0006-2952(89)90238-4subject
Has Abstractpub_date
1989-03-01 00:00:00pages
831-6issue
5eissn
0006-2952issn
1873-2968pii
0006-2952(89)90238-4journal_volume
38pub_type
杂志文章abstract：:Microsomal epoxide hydrolase (mEH) catalyzes the hydrolysis of epoxide intermediates derived from drugs and environmental chemicals. The response of in vivo (embryo) and in vitro (embryo fibroblast) tests were analyzed using mEH-null and wild-type mice to determine the relative role of maternal and embryonic mEH in th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)00847-x
更新日期：2002-03-15 00:00:00
abstract：:The 5-HT1A receptor is a critical mediator of serotonergic (5-HT) function. We have identified 13 potential single nucleotide polymorphisms resulting in amino acid changes throughout the human 5-HT1A receptor. The pharmacological profiles of these 13 polymorphic variants were then characterized using a high-throughput...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2003.09.030
更新日期：2004-02-01 00:00:00
abstract：:The mechanism for formation of high-affinity binding of 1-(2,6-dichlorobenzylidene-amino)-3-hydroxyguanidine (guanoxabenz) to alpha2-adrenoceptors was studied in particulate fractions from the rat spleen. The proportion of apparent high versus low-affinity alpha2-adrenoceptor binding sites increased with increasing in...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00135-x
更新日期：1998-11-01 00:00:00
abstract：:The multidrug resistance (MDR) phenotype is the major cause of failure of cancer chemotherapy. This phenotype is mainly due to the overexpression of the human MDR1 (hMDR1) gene. Several studies have shown that transcriptional regulation of this gene is unexpectedly complex and is far from being completely understood. ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(02)01156-5
更新日期：2002-09-01 00:00:00
abstract：:Gastric cancer is the third common cause of cancer mortality in the world with poor prognosis and high recurrence due to lack of effective medicines. Our studies revealed that lanatoside C, a FDA-approved cardiac glycoside, had an anti-proliferation effect on different human cancer cell lines (MKN-45; SGC-7901; HN4; M...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.02.023
更新日期：2018-04-01 00:00:00
abstract：:Steroidal and non-steroidal antioestrogens, steroidal compounds with (disubstituted) dialkyl amino side chain, cholesterol derivatives, histaminic and (anti)-progestational compounds were tested for their ability to compete with [3H]tamoxifen for the specific antioestrogen binding site (AEBS) in the post-mitochondrial...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90138-9
更新日期：1992-06-23 00:00:00
abstract：:Administration of phenobarbital to chick embryos increased hepatic microsomal UDP-glucuroyltransferase activity some 25-fold. The large phenobarbital-induced increase of UDP-glucuronyltransferase activity was correlated to an equivalent increase of immunochemically measurable UDP-glucuronyltransferase protein. Poly(A+...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90159-0
更新日期：1986-04-01 00:00:00
abstract：:Heme oxygenase 1 (HO-1) is a stress protein and has been suggested to provide defense mechanisms against agents that may induce oxidative injury. Vitamin E (VE) is considered to function as an important cellular antioxidant. Rats were fed a VE-deficient (0E) or a VE-sufficient (10E) diet for 6 weeks and then were intr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00302-x
更新日期：1997-11-15 00:00:00
abstract：:We investigated the interactions of 4'-(9-acridinylamino)methanesulfon-m-anisidide (mAMSA) with thiol-containing compounds and the potential binding of the thiolytic adducts to DNA. All thiols tested (glutathione, cysteine, coenzyme A, 2-mercaptoethanol and lactate dehydrogenase) formed adducts with mAMSA as evidenced...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90319-9
更新日期：1986-05-15 00:00:00
abstract：:Exogenous phosphatidic acid (PA) was observed to produce a concentration-dependent increase in [Ca(2+)](i) in cultured A10 vascular smooth muscle cells. Preincubation of cells with sarcoplasmic reticulum Ca(2+)-ATPase inhibitors (cyclopiazonic acid and thapsigargin), a phospholipase C inhibitor (2-nitro-4-carboxypheny...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00201-6
更新日期：2003-06-15 00:00:00
abstract：:Magnesium-pyridoxal-5'-phosphate-glutamate (MPPG) has been shown to ameliorate atherosclerotic symptoms in rabbits. In vitro, MPPG in the presence of peroxides such as cholesterolhydroperoxide or cumene hydroperoxide and Mn2+ ions produces "excited states" measurable as chemiluminescence or ethylene release from 1-ami...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90442-l
更新日期：1992-08-04 00:00:00
abstract：:The (Na+ + K+)-ATPase is localized to the cerebral endothelium, i.e. the blood-brain barrier, and is important for the maintenance of the brain electrolyte environment. Data from the present study indicate that Pb2+ inhibits the binding of [3H]ouabain to the cerebral microvascular (Na+ + K+)-ATPase in a time- and dose...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90606-l
更新日期：1990-06-15 00:00:00
abstract：:Spin traps are increasingly employed in the detection of free radicals in biological systems, including liver microsomes and isolated hepatocytes. Two spin traps phenyl-t-butyl nitrone (PBN) and 4-pyridyl-l-oxide-t-butyl nitrone (4-POBN) have been tested for their effects on hepatocyte viability and mixed-function oxi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90010-9
更新日期：1986-11-15 00:00:00
abstract：:Rat liver microsomes and purified NADPH-cytochrome c reductase metabolized [14C]misonidazole anaerobically to a reactive intermediate that covalently binds to tissue macromolecules. Air strongly inhibited the binding whereas carbon monoxide had no effect, indicating that misonidazole is activated via reduction and not...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90158-7
更新日期：1982-02-15 00:00:00
abstract：:There is intense interest in the development and application of animal models of CNS disorders to explore pathology and molecular mechanisms, identify potential biomarkers, and to assess the therapeutic utility, estimate safety margins and establish pharmacodynamic and pharmacokinetic parameters of new chemical entiti...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2013.06.016
更新日期：2014-01-01 00:00:00
abstract：:Protein phosphatases are responsible for keeping the signaling output of stimulus-activated protein kinases in check; but protein phosphatases are also themselves targets and conveyors of biological signals. Among the major serine/threonine phosphatases, protein phosphatase 2A (PP2A) appears to play a privileged role ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(98)00245-7
更新日期：1999-02-15 00:00:00
abstract：:Metamizole is an analgesic and antipyretic, but can cause neutropenia and agranulocytosis. We investigated the toxicity of the metabolites N-methyl-4-aminoantipyrine (MAA), 4-aminoantipyrine (AA), N-formyl-4-aminoantipyrine (FAA) and N-acetyl-4-aminoantipyrine (AAA) on neutrophil granulocytes and on HL60 cells (granul...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.01.011
更新日期：2019-05-01 00:00:00
abstract：:The effects of propranolol or phentolamine on the metabolism of phospholipids, diacylglycerol, and triacylglycerol were studied in the bovine retina in vitro. Lipid labeling was followed during short-term incubation of intact bovine retinas with [U-14C]glycerol and [1-14C]palmitic acid. Each of these precursors was re...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90341-0
更新日期：1982-03-15 00:00:00
abstract：:The localization of [3H]forskolin binding to microscope slide mounted sections of rat kidney has been examined using autoradiography. Saturation studies showed [3H]forskolin binding to two sites, a high affinity site (KD = 8.7 nM, Bmax = 0.14 pmol/mg protein) and a low affinity site (KD = 6.7 microM, Bmax = 11.0 pmol/...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90280-x
更新日期：1990-03-15 00:00:00
abstract：:Tannins are polyphenols commonly found in plant-derived foods. When ingested they can have various harmful effects, but salivary proline-rich proteins (PRPs) may provide protection against dietary tannins. The aim of this study was to investigate whether basic PRPs, a major family of salivary proteins, can prevent int...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.02.013
更新日期：2006-05-28 00:00:00
abstract：:Liver mitochondrial low-Km aldehyde dehydrogenase (ALDH2, EC 1.2.1.3), the isoform responsible for the conversion of acetaldehyde to acetate, is inhibited by the sulfoxide bioactivation products of Et2NC(O)SMe (from the alcohol aversion drug disulfiram), Pr2NC(O)SEt (the herbicide S-ethyl N,N-dipropylthiocarbamate), a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00239-7
更新日期：1999-11-01 00:00:00
abstract：:Folate-binding protein (FBP), a high-affinity folate receptor, is responsible for cellular accumulation of folate and folate analogs such as methotrexate in human KB (nasopharyngeal carcinoma) cells. Both FBP and FBP mRNA increase 3- to 5-fold when KB cells are grown in folate-deficient (less than 10 nM folate) medium...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90235-o
更新日期：1993-06-22 00:00:00
abstract：:During a cellular screening of thiocolchicine analogs, thiocolchicine dimers resulted particularly active in cisplatin-resistant A2780-CIS cells. In order to discover by which mechanism(s) thiocolchicine dimers overcame cisplatin resistance, p53, p21waf1 and MLH1 were assessed by Western blot. Results pointed out that...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.09.004
更新日期：2005-01-01 00:00:00
abstract：:Despite the substantial progress made in understanding initiation expression of the MOR gene in lymphocytes, the signal pathway associated with MOR gene transcription remains to be better defined. As the phosphatidylinositol 3-kinase (PI3K)/AKT pathway can mediate diverse biological responses and is crucial for optima...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.09.013
更新日期：2010-02-01 00:00:00
abstract：:Diabetic nephropathy (DN) is one of the most prevalent lethal complications of diabetes that leads to end stage renal disease. Although several clinical approaches exist to attenuate DN, there is not curative treatment to date. DN is complicated, as it involves several simultaneous molecular pathways. Some natural and...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2018.06.017
更新日期：2018-09-01 00:00:00
abstract：:An enzyme (NADPH-dependent diaphorase) present in rat brain microsomes has been solubilised and shown to utilise both nitrobluetetrazolium and cytochrome c as electron acceptors, when reduced by NADPH. The kinetics of the enzyme have been determined using cytochrome c (Km = 1.3 microM), NADPH (Km = 1.4 microM) and the...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90302-4
更新日期：1988-08-15 00:00:00
abstract：:The effects of 3-monoalkyl- and 3,5-dialkyl-substitution on the cytotoxicity of paracetamol (PAR) in rat hepatocytes was studied. PAR is known to be bioactivated by the hepatic microsomal cytochrome P-450 containing a mixed-function oxidase system presumably to N-acetyl-para-benzoquinone imine (NAPQI), a reactive meta...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90653-2
更新日期：1986-11-01 00:00:00
abstract：:This article has been retracted consistent with Elsevier Policy on Article Withdrawal. Please see . The Publisher apologises for any inconvenience this may cause. ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.03.026
更新日期：2006-04-18 00:00:00
abstract：:It was shown previously that three 1,5-diazabicyclo[3.1.0]hexane-2,4-diones selectively inhibited human Type II IMP dehydrogenase (IMPDH) from Tmolt4 cell leukemia [Barnes et al., Biochemistry 2000;39:13641-50]. The agents acted as competitive inhibitors of this isoform, yet when tested against human Type I at concent...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00649-9
更新日期：2001-07-01 00:00:00
abstract：:Intracellular GSH has some effects on protecting cells against cadmium and is involved in the development of resistance to cisplatin (CDDP). To determine the effects of intracellular GSH on expression of the heat shock genes (hsp) induced by cadmium in CDDP-resistant cancer cells, we used two human ovarian cancer cell...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00049-0
更新日期：1999-07-01 00:00:00
