Abstract:
:Diethyldithiocarbamate-methyl ester (DDTC-Me), a metabolite of disulfiram, has been shown recently to produce a disulfiram-ethanol reaction (DER). Studies were carried out to compare the ethanol-sensitizing properties of DDTC-Me with those of disulfiram and diethyldithiocarbamate (DDTC) in the rat. All three drugs inhibited liver mitochondrial low Km aldehyde dehydrogenase (ALDH) in vivo, with maximal ALDH inhibition occurring 8 hr after drug administration. The onset of ALDH inhibition was most rapid after DDTC-Me administration. ALDH was inhibited approximately 50% 0.5 hr after DDTC-Me, whereas ALDH was inhibited only 5 and 10%, respectively, after disulfiram and DDTC. Not until 8 hr after drug treatment was ALDH inhibition the same for disulfiram, DDTC and DDTC-Me. The degree of ALDH inhibition from 8 to 172 hr after dosing was the same for all three drugs. An ethanol (1 g/kg, 20% v/v) challenge administered to rats treated with disulfiram (75 mg/kg), DDTC (114 mg/kg), or DDTC-Me (41.2 mg/kg) for 8 hr produced similar blood acetaldehyde/ethanol concentration-time profiles. In addition, all three agents produced a DER (hypotension, tachycardia). No DER occurred if ethanol was administered more than 24 hr after drug pretreatment. The hypotension associated with the DER correlated with the increased blood acetaldehyde but not blood ethanol. A threshold blood acetaldehyde of 110 microM appeared to be required for hypotension to occur, and this was related to ALDH inhibition of approximately 40%. The tachycardia associated with the DER correlated more with blood ethanol. After DDTC-Me administration, no disulfiram or DDTC could be detected in the plasma. Furthermore, no DDTC-Me was found in the plasma 8 hr after DDTC-Me administration, suggesting that no correlation exists between the DER and plasma concentration of DDTC-Me and most likely disulfiram. These data suggest that the alcohol-sensitizing properties of DDTC-Me are similar to those observed with disulfiram and DDTC. Since DDTC-Me is an active metabolite and more potent than disulfiram and DDTC in producing a DER, disulfiram metabolism is an important consideration in the disulfiram-ethanol reaction.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Yourick JJ,Faiman MDdoi
10.1016/0006-2952(89)90380-8subject
Has Abstractpub_date
1989-02-01 00:00:00pages
413-21issue
3eissn
0006-2952issn
1873-2968pii
0006-2952(89)90380-8journal_volume
38pub_type
杂志文章abstract::In model experiments using human erythrocytes, glycochenodeoxycholate caused extensive membrane damage (as judged by release of membrane phospholipid and acetylcholinesterase and by cell lysis) at approximately 10-fold lower concentrations than glycocholate. Chenodeoxycholate feeding had no effect upon the total prote...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90660-9
更新日期:1984-07-15 00:00:00
abstract::Incubation of adriamycin resistant Chinese hamster lung cells with the calmodulin inhibitor trifluoperazine (TFP) resulted in a significant increase in the cellular accumulation of drug. When resistant cells were prelabeled with 32Pi and then treated with TFP, a major increase also occurred in the phosphorylation of a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90686-0
更新日期:1985-05-01 00:00:00
abstract::This study was designed to examine the relationship between the extent of Sandimmun (cyclosporin A, SIM) metabolism and SIM-induced hepatotoxicity both in vivo and in primary cultures of rat hepatocytes. Firstly, SIM (50 mg/kg p.o.) was administered daily to male Wistar rats for 10 days with or without co-administrati...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90024-f
更新日期:1990-01-15 00:00:00
abstract::BAY X 1005 ((R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid) has been demonstrated to be a potent inhibitor of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) synthesis in various in vitro systems. Using mainly human polymorphonuclear leukocytes (PMNL) this study elucidates the mech...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90382-7
更新日期:1993-01-07 00:00:00
abstract::The inhibition of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide anion (O2(.-)) generation by 2-benzyloxybenzaldehyde (CCY1a) was investigated in rat neutrophils, and the underlying mechanism of this inhibition was assessed. CCY1a concentration-dependently inhibited O2(.-) generation (IC(50)=18.5+/-4....
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00006-6
更新日期:2003-04-01 00:00:00
abstract::Prostaglandin synthetase has the ability to catalyze the metabolism of paracetamol to a reactive metabolite, which binds to protein and reduced glutathione (GSH). This was demonstrated with microsomes isolated from both sheep seminal vesicles (SSV) and rabbit kidney medulla. The activation of paracetamol occurred thro...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90029-6
更新日期:1982-04-01 00:00:00
abstract::5-Substituted-2,2'-anhydrouridines are a new class of competitive inhibitors of uridine phosphorylase. The most potent member of the series is 2,2'-anhydro-5-ethyluridine with an apparent Ki value of 25 nM. These compounds are selective inhibitors of uridine phosphorylase and have no effect on thymidine phosphorylase....
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90643-4
更新日期:1985-05-15 00:00:00
abstract::The effects of thromboxane A2 (TXA2) on the proliferation of vascular smooth muscles cells (VSMC) were examined using primary cultures of VSMC from rat aorta. U46619, a stable TXA2 mimetic, stimulated DNA synthesis of VSMC only in the presence of insulin. The effect was concentration-dependent with a half-maximal effe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90096-4
更新日期:1990-12-01 00:00:00
abstract::Parkin (PRKN) is a ubiquitin E3 ligase that catalyzes the ubiquitination of several proteins. Mutations in the human Parkin gene, PRKN, leads to degeneration of dopaminergic (DA) neurons, resulting in autosomal recessive early-onset parkinsonism and the loss of PRKN function is linked to sporadic Parkinson's disease (...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.08.002
更新日期:2019-10-01 00:00:00
abstract::We have generated and characterised a clone of chicken DT40 lymphocytes stably transfected with the rat P2X(7) receptor (rP2X(7)). Successful transfection was confirmed by Western blotting. Under voltage clamp, P2X(7)-expressing cells responded to ATP and dibenzoyl-ATP (Bz-ATP) (a more potent P2X(7) receptor agonist) ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00286-7
更新日期:2003-08-01 00:00:00
abstract::Breast cancer is the leading cause of cancer death among females, and novel chemotherapeutic drugs for treating breast cancer are needed urgently. Saxifragifolin D (SD) was isolated by our group from Androsace umbellata which is commonly used to treat solid tumor. In this study, we evaluated its growth inhibitory effe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.01.009
更新日期:2013-04-01 00:00:00
abstract::The effect of loxoprofen-Na, a novel non-steroidal anti-inflammatory drug with a prodrug property, on prostaglandin (PG) levels in the inflammatory tissue was investigated with a carrageenin-induced pleurisy model in rats. The intrapleural injection of carrageenin caused a marked increase in the levels of PGE2 and 6-k...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90242-w
更新日期:1991-11-27 00:00:00
abstract::The cytochrome P450-dependent metabolism of benzo(a)pyrene and other xenobiotics has been investigated in liver microsomes prepared from a local marine safi fish, Siganus canaliculatus. The safi fish was found to have a well-developed microsomal monooxygenase system consisting of cytochrome P450, cytochrome b5 and NAD...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)84544-8
更新日期:1995-10-26 00:00:00
abstract::Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Recently, isothiocyanate...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.03.044
更新日期:2004-09-15 00:00:00
abstract::Treatment of immature 21-day-old female Sprague-Dawley rats with 17 beta-estradiol (E2) (0.5 microgram/rat) caused a significant increase in uterine wet weight, DNA synthesis, progesterone receptor (PR) binding, and peroxidase activity. At doses as high as 40 mg/rat, the bioflavonoid naringenin did not cause a signifi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02061-6
更新日期:1995-10-26 00:00:00
abstract::Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side popul...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2012.04.010
更新日期:2012-08-01 00:00:00
abstract::3 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1.50) of rat liver cytosol catalyzes the second step in glucocorticoid metabolism, namely the NADPH-dependent reduction of 5 beta-dihydrocortisol to tetrahydrocortisol. The purified enzyme is potently inhibited by the nonsteroidal anti-inflammatory drugs [Penning and Talala...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90696-9
更新日期:1986-12-01 00:00:00
abstract::The effect of glutathione depletion on cytotoxicity of the anthracycline daunorubicin, and of a copper:bis-thiosemicarbazone chelate, was examined in the P388 murine leukemia and its anthracycline-resistant subline, P388/ADR. Depletion of intracellular glutathione was accomplished through exposure to buthionine sulfox...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90430-2
更新日期:1986-10-01 00:00:00
abstract::The stimulated uptake of 45Ca2+ into incubated cerebrocortical synaptosomes caused by veratrine (75 microM) was blocked by low concentrations of verapamil (0.5-30 microM) which did not prevent or reduce depolarization as judged by efflux of potassium (K+). However, verapamil did not prevent amino acid neutrotransmitte...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90314-4
更新日期:1985-06-01 00:00:00
abstract::The pharmacokinetics and biochemical effects of the uridine phosphorylase (UrdPase) inhibitor 5-benzylacyclouridine (BAU) were investigated in the mouse, rat and monkey. Following i.p. administration of BAU (30 mg/kg) in the mouse and i.v. administration in the rat and monkey, initial BAU plasma half-life values were ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90390-i
更新日期:1993-01-07 00:00:00
abstract::Cyclodextrins generally exhibit hemolytic activity, some at concentrations as low as 1-10 mg/mL or lower. However, we found previously that a highly polysulfated cyclodextrin has no demonstrable hemolytic activity (Macarak et al., Biochem Pharmacol 42: 1502-1503, 1991). In the present study, we determined that, in fac...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90244-q
更新日期:1993-03-09 00:00:00
abstract::The nicotinic acetylcholine receptors (nAChR) assembled from alpha4 and beta2 subunits are the most densely expressed subtype in the brain. Concentration-effect curves for agonist activation of alpha4beta2*-nAChR are biphasic. This biphasic agonist sensitivity is ascribed to differences in subunit stoichiometry. The s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.06.040
更新日期:2010-10-15 00:00:00
abstract::The effects of the basic polypeptide melittin on islet phospholipid degradation and insulin release were studied in static incubations of intact rat islets as a possible model of endogenous phospholipase A2 (PLA2) activation. Melittin (2 micrograms/ml) increased [3H]-arachidonic acid [( 3H]-AA) release from prelabeled...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90438-7
更新日期:1986-10-01 00:00:00
abstract::Regenerating liver from partial hepatectomy (HPX) is known to exhibit a strong and transient deficiency in both spectrally detectable microsomal cytochrome P-450 (P-450) and related monooxygenase activities. Male Wistar rats (250-300 g) were HPX or sham operated and liver was excised at different times after operation...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90705-8
更新日期:1988-09-15 00:00:00
abstract::Exposure to ultraviolet B (UVB) irradiation induces acute skin inflammation such as erythema (sunburn) and edema, and prostaglandin (PG)E2 in the epidermis plays an important role as its prominent mediator. In the present study, we investigated the effect of nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) from Citrus de...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.04.006
更新日期:2004-08-01 00:00:00
abstract::Tetraalkylammonium salts having n-propyl to n-amyl side chains inhibited rat liver sulfotransferase (ST) activities toward dehydroepiandrosterone and cortisol, but not ST activity toward 2-naphthol, whereas trialkylamines having ethyl to n-amyl side chains inhibited ST activity toward dehydroepiandrosterone, but not S...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)00495-8
更新日期:1995-03-01 00:00:00
abstract::Pancreatic stellate cells (PSCs) play a key role in pancreatic fibrosis, a constant feature of chronic pancreatitis. PSC activation occurs in response to profibrogenic mediators such as cytokines and involves proliferation, transition towards a myofibroblastic phenotype and enhanced production of extracellular matrix ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00075-3
更新日期:2003-04-15 00:00:00
abstract::Tumor-induced neoangiogenesis is an essential event for solid tumor growth. Therefore, a compound able to block angiogenesis-promoting factors could have antitumor activity. The polysulfonated naphthylurea suramin is hypothesized to have this mode of action. A series of sulfonated distamycin A derivatives have been sy...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90020-5
更新日期:1994-01-20 00:00:00
abstract::The effect of deferoxamine on nucleotide metabolism in HL-60 leukemic cells was studied to explore the mechanism of its antiproliferation activity. It was found that in intact cells deferoxamine markedly inhibited the ribonucleotide reduction and incorporation of bases (adenine, hypoxanthine), ribonucleosides (inosine...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90601-0
更新日期:1987-07-15 00:00:00
abstract::The formation of morphine glucuronides is enantio- and regioselective in rats and humans. In rat liver microsomes, natural (-)-morphine formed only the 3-O-glucuronide, whereas the unnatural (+)-morphine formed glucuronides at both the 3-OH and 6-OH positions, with the 6-O-glucuronide being the principal product. In h...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90625-4
更新日期:1989-10-01 00:00:00