Abstract:
:Tianeptine is a new tricyclic antidepressant which is metabolized mainly by beta-oxidation of its heptanoic side chain. We determined the effects of tianeptine on the mitochondrial oxidation of natural fatty acids in mice. In vitro, tianeptine (0.5 mM) inhibited by only 32% the formation of beta-oxidation products from [1-14C]palmitic acid by hepatic mitochondria, but inhibited by 71% that from [1-14C]octanoic acid and by 51% that from [1-14C]butyric acid. The activity of the tricarboxylic acid cycle, assessed as the in vitro formation of [14C]CO2 from [1-14C]acetylcoenzyme A was decreased by 51% in the presence of tianeptine (0.5 mM). The inhibition of both beta-oxidation and the tricarboxylic acid cycle appeared reversible in mitochondria from mice exposed to tianeptine in vivo but incubated in vitro without tianeptine. In vivo, administration of tianeptine (0.0625 mmol/kg i.p.), decreased by 53 and 58%, respectively, the formation of [14C]CO2 from [1-14C]octanoic acid and [1-14C]butyric acid, but did not significantly decrease that from [1-14C]palmitic acid. After administration of high doses of tianeptine, however, formation of [14C]CO2 from [1-14C]palmitic acid became inhibited as well, transiently after 0.25 mmol/kg and durably (greater than 24 hr) after 0.75 mmol/kg i.p. Hepatic triglycerides were increased 24 hr after administration of 0.75 mmol/kg i.p. of tianeptine, but not after 0.25 mmol/kg i.p. Microvesicular steatosis of the liver was observed in some mice after 0.75 mmol/kg i.p., but not after 0.5 mmol/kg i.p. We conclude that tianeptine inhibits the oxidation of medium- and short-chain fatty acids in mice. Microvesicular steatosis, however, requires very large doses in mice (0.75 mmol/kg i.p., i.e. 600-times the oral dose in humans), and is therefore unlikely to occur in humans.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Fromenty B,Freneaux E,Labbe G,Deschamps D,Larrey D,Letteron P,Pessayre Ddoi
10.1016/0006-2952(89)90580-7subject
Has Abstractpub_date
1989-11-01 00:00:00pages
3743-51issue
21eissn
0006-2952issn
1873-2968pii
0006-2952(89)90580-7journal_volume
38pub_type
杂志文章abstract::Pretreatment of NG108-15 cells with 0.03-25 microM prostaglandin E1 (PGE1) produced decreases in the maximal stimulation of adenylate cyclase activity produced by iloprost, N-ethylcarboxamidoadenosine and sodium fluoride. The rate of desensitization to all three agents was dependent on the concentration of PGE1 used, ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90405-7
更新日期:1994-03-15 00:00:00
abstract::ATP-driven efflux pumps such as phosphoglycoprotein-170 (P-gp), multidrug-resistance-associated protein-2 (MRP-2), or breast cancer resistance protein (BCRP) play a crucial role in limiting the efficacy of tumor pharmacotherapy. Selected flavonoids have been suggested to inhibit individual efflux-transporters and to a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.04.038
更新日期:2010-08-15 00:00:00
abstract::Previous studies from this lab and others have demonstrated that nitric oxide (NO) in a concentration dependent manner, modulated neutrophil and leukemic cell survival. Subsequent studies delineated importance of iNOS in neutrophil differentiation and leukemic cell death. On the contrary, role of nNOS in survival of t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.113779
更新日期:2020-06-01 00:00:00
abstract::The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox-sensitive transcription factors such as nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1), which regulate the genes for proinflammatory mediators and protective antioxidant genes. GSH, a ubiquitous tripeptide t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(00)00392-0
更新日期:2000-10-15 00:00:00
abstract::Male mice were exposed via their diet to perfluoro fatty acids of various chain-lengths (2-10 carbon atoms) at different doses (0.02 and 0.1% weight) and for different periods of time (2-10 days). Thereafter, we monitored effects on liver and body weights and a number of hepatic parameters, including mitochondrial pro...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90383-t
更新日期:1992-09-25 00:00:00
abstract::The growth inhibitory effects of 5-fluorouracil (FUra) or 5-fluoro-2'-deoxyuridine (FdUrd) combined with 5-methyltetrahydrofolate (5-CH3-H4PteGlu) were determined, as a function of time, dose, and sequence of exposure, on human T-lymphoblast leukemia cells, CCRF-CEM. Synergistic inhibitory effects on cell growth were ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90201-2
更新日期:1987-09-15 00:00:00
abstract::The in vitro inhibition of the cytochrome P-450 (P-450) isozyme specific positional hydroxylation of androst-4-ene-3,17-dione (androstenedione) by the alkylamino containing compounds trans- and cis-tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, SKF 525-A and the non-alkylamino containing compounds tamoxifen meta...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90168-8
更新日期:1989-01-01 00:00:00
abstract::The chemotherapeutic drug cisplatin is an important treatment for many types of solid tumours, in particular non-small cell lung cancer (NSCLC). Platinum(IV) complexes offer several advantages to cisplatin due to their requirement for reduction to the active platinum(II) form to elicit cytotoxicity. This should minimi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.07.016
更新日期:2005-10-15 00:00:00
abstract::The present investigation addressed the role of verapamil for oral pharmacokinetics of morphine-6-beta-glucuronide (M6G). Male Sprague-Dawley rats received 62.5 mg kg(-1) M6G-dihydrate orally w/wo pre-treatment with 70 mg kg(-1) verapamil. Intravenous M6G (3.9 mg kg(-1) ) and oral morphine (52.7 mg kg(-1) morphine-hyd...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)00881-x
更新日期:2002-04-15 00:00:00
abstract::Cyclophosphamides are pro-drugs whose killing agent is produced from an aldehyde that is formed by the action of a P450 oxidation step. The mustard from the aldehyde can destroy bone marrow cells as well as the tumor. Aldehyde dehydrogenase (EC 1.2.1.3) can oxidize the aldehyde and hence inactivate the cytotoxic inter...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.06.018
更新日期:2008-09-01 00:00:00
abstract::The tissue distribution of captopril, an antihypertensive drug possessing a free sulfhydryl group, and its sulfur-conjugated metabolites was studied in rats by gas chromatography-mass spectrometry at 15, 30 and 60 min following a single 10 mg/kg oral dose of captopril. It was found that tissue accumulation of captopri...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90328-3
更新日期:1983-05-15 00:00:00
abstract::To investigate the hypothesis that cyclic AMP (cAMP) regulates arachidonic acid metabolism in vascular tissue, we have studied the effects of forskolin (FSK), an activator of adenylate cyclase, and 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, on hormone-stimulated prostacyclin (PGI2) synthesis in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90109-1
更新日期:1985-01-01 00:00:00
abstract::Glutathione conjugation and transportation of glutathione conjugates of anticancer drugs out of cells are important for detoxification of many anticancer drugs. Inhibition of this detoxification system has recently been proposed as a strategy to treat drug-resistant solid tumors. Gallbladder carcinoma is resistant to ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.12.006
更新日期:2010-04-15 00:00:00
abstract::Antibody-directed enzyme prodrug therapy (ADEPT) aims at the specific activation of a prodrug by an enzyme-immunoconjugate localized in tumor tissue. The use of an enzyme of human origin is preferable in ADEPT because it might not be immunogenic when administered to patients. In the case of human beta-glucuronidase, p...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)00248-1
更新日期:1996-08-09 00:00:00
abstract::The response and engagement of host normal tissues in malignant disease are major factors in therapeutic resistance. Physically, solid tumors have regions of hypoxia and acidosis. These physical stresses can lead to a more aggressive malignant phenotype through activation of HIF, GLUT-1, carbonic anhydrase IX, and sub...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2009.01.006
更新日期:2009-06-01 00:00:00
abstract::The discovery of caspase activation counts as one of the most important finds in the biochemistry of apoptosis. However, targeted disruption of caspases does not impair every type of apoptosis. Other proteases can replace caspases and several so called "caspase independent" pathways are now described. Here we review o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2008.07.039
更新日期:2008-12-01 00:00:00
abstract::Using the incorporation of [3H]isoleucine or [3H]hypoxanthine into acid-insoluble products as indices of protein- and nucleic acid-synthetic activity, respectively, it was shown that seven plant-derived quassinoids with differing chemical substitutions all inhibited protein synthesis more rapidly than nucleic acid syn...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90644-8
更新日期:1989-12-15 00:00:00
abstract:BACKGROUND:Rho-Associated kinases ROCK1 and ROCK2 have been extensively investigated in the pathogenesis of cardiovascular disease. However, their roles are not fully understood in carcinogenesis. In this study, we investigated whether ROCK1 or ROCK2 is required for the survival and growth of hepatocellular carcinoma (...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114353
更新日期:2020-12-02 00:00:00
abstract::The nitroderivative 1-nitro-2-phenylethane (NPE) was recently described as a compound possessing heme-dependent soluble guanylyl cyclase (sGC) stimulating properties in vascular smooth muscle cells. In this study, we tested such pharmacological property of NPE in mice pancreatic acinar cells subjected to the bile salt...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.07.030
更新日期:2014-09-15 00:00:00
abstract::The pharmacological properties of the human D2L (long isoform) and rat D3 dopamine receptors in functional assays were examined. A range of dopamine agonists were assessed for their ability to inhibit adenosine 3'5'-cyclic monophosphate (cAMP) accumulation via the two receptors expressed stably in Chinese hamster ovar...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00101-x
更新日期:1999-07-15 00:00:00
abstract::Multidrug resistance (MDR) is a phenomenon where cancer cells become simultaneously resistant to anticancer drugs with different structures and mechanisms of action. MDR has been shown to be associated with overexpression of ATP-binding cassette (ABC) transporters. Here, we report that telatinib, a small molecule tyro...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.02.012
更新日期:2014-05-01 00:00:00
abstract::Glyburide is a second-generation sulfonylurea hypoglycemic drug used for the treatment of select women with pregestational and gestational diabetes mellitus (GDM). In vitro and in vivo investigations demonstrated its very low transplacental transfer to the fetal circulation. However, the factors influencing its low tr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.05.019
更新日期:2006-08-28 00:00:00
abstract::African trypanosomes, like Trypanosoma brucei, depend on antigenic variation to evade the immune response of the vertebrate host. An antigenic switch corresponds to the activation of a variable surface glycoprotein (VSG) gene from a large silent repertoire. Most switches require the duplicative transposition of a VSG ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90208-4
更新日期:1985-12-01 00:00:00
abstract::When human saliva obtained after cigarette smoking was incubated in the presence of tryptamine, the formation of 1,2,3,4-tetrahydro-beta-carboline (TBC) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline (MTBC) was observed in a short time. After incubation with tryptamine (2.5 micrograms/microliter) for 10 min, the conce...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02068-3
更新日期:1995-12-22 00:00:00
abstract::In vitro absorption of three angiotensin converting enzyme (ACE) inhibitors, captopril, enalapril and lisinopril, and their stabilities in aqueous buffer as well as their resistance to intestinal and dermal tissue homogenates were investigated. The results demonstrate that the spontaneous oxidation of captopril, enala...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90382-4
更新日期:1994-03-29 00:00:00
abstract::The effect of oxidant stress produced by redox cycling of substituted 1,4-naphthoquinones on the activity of platelet (Na(+)-K+)ATPase and the active transport of serotonin (5-HT) was studied. 2-Methyl-1,4-naphthoquinone (menadione) produced a concentration-dependent (0-100 microM) and time-dependent (2-20 min) stimul...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90203-h
更新日期:1991-03-15 00:00:00
abstract::The addition of agents, such as tumor necrosis factor-alpha, to human peripheral neutrophils (HPPMN) induces priming, which enhances the receptor-mediated superoxide (O2-) generation and tyrosine phosphorylation of several HPPMN proteins. Lidocaine, a local anesthetic, inhibited both enhanced O2- generation and tyrosi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90299-c
更新日期:1993-04-22 00:00:00
abstract::The pyridazinone derivative zardaverine has recently been introduced as a potent bronchodilator in vivo and in vitro. In addition, zardaverine exerts a positive inotropic action on heart muscle in vitro. The actions of zardaverine are thought to be mediated via inhibition of phosphodiesterase (PDE) activity. Recent da...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90694-z
更新日期:1991-06-21 00:00:00
abstract::Two pyrophosphate analogues, dichloromethane diphosphonate (Cl2MDP), and 1-hydroxyethane-1,1-diphosphonate (EHDP), at concentrations of 0.5-1 mM, efficiently inhibited the growth of amoebae of the slime mould Dictyostelium discoideum. Cell viability decreased markedly upon incubation with the diphosphonates. The mecha...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90342-g
更新日期:1992-12-01 00:00:00
abstract::We have demonstrated that the simplest steady-state random sequential Bi Bi mechanism is sufficient to explain the previously reported non-hyperbolic kinetics of glutathione S-transferase 3-3 [Pabst MJ et al., J Biol Chem 249: 7140-7150, 1974; Jakobson I et al., Biochem J 177: 861-868, 1979]. The metabolism of 1-chlor...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90621-q
更新日期:1990-06-15 00:00:00