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1.
Acta Microbiol Immunol Hung ; 51(1-2): 75-83, 2004.
Article in English | MEDLINE | ID: mdl-15362289

ABSTRACT

The antipsychotic phenothiazine triflupromazine, possessing a methyl-thio substituent at position 10 and a fluorine moiety at position 2, exhibited significant antibacterial activity against 279 strains of Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) of the drug, according to the agar dilution method, was between 2 and 50 microg/ml for Staphylococcus aureus, and 5 and 100 microg/ml for shigellae and vibrios. Triflupromazine, when injected intraperitoneally into Swiss albino mice at a concentration of 30 microg/mouse (20 g), manifested a significant protection to the mice (p<0.001) when they were challenged with 50 median lethal dose (MLD) of Salmonella typhimurium NCTC 74. Moreover, there was a statistically significant reduction in the number of viable bacteria in organ homogenates and blood of mice treated with this phenothiazine compound.


Subject(s)
Anti-Infective Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Triflupromazine/pharmacology , Animals , Anti-Infective Agents/administration & dosage , Humans , Male , Mice , Microbial Sensitivity Tests , Salmonella Infections, Animal/drug therapy , Salmonella typhimurium/drug effects , Triflupromazine/administration & dosage
2.
Arterioscler Thromb Vasc Biol ; 23(11): 2048-54, 2003 Nov 01.
Article in English | MEDLINE | ID: mdl-12969989

ABSTRACT

OBJECTIVE: This study was undertaken to assess the role of vascular smooth muscle cell (VSMC) Ca2+ channels and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in gene regulation after oxidative endothelial injury (OEI). METHODS AND RESULTS: OEI was produced by infusion of Na fluorescein (NaFluo) photoactivated by UV light immediately before intravenous injection. Posterior cerebral arteries were studied using immunofluorescence imaging, Western blotting, or patch clamping of isolated cells. After infusion of photoactivated NaFluo, but not NaFluo, (1) superoxide dismutase-1 (SOD-1) was upregulated in endothelium, consistent with oxidant stress; (2) the fraction of VSMC nuclei labeled for proliferating cell nuclear antigen (PCNA) increased 7-fold at 6 hours, preceded by a several-fold increase in nuclear phospho-cAMP-response element binding protein, with PCNA upregulation prevented by pretreatment with polyethylene glycol (PEG)-SOD; (3) in VSMCs, phospho-CaMKII increased 20-fold 5 minutes after OEI, with a 2-fold increase in peak Ca2+ channel currents; and (4) changes in cAMP-response element binding protein and PCNA were blocked by systemic administration of lipophilic (nifedipine) or hydrophilic (amlodipine) 1,4-dihydropyridine Ca2+ channel blockers, the calmodulin inhibitor trifluoperazine, or the CaMKII inhibitor KN-93, with none of these agents preventing SOD-1 upregulation in endothelium. CONCLUSIONS: Activation of VSMC Ca2+ channels and CaMKII is a key early signaling event required for upregulation of PCNA gene expression in VSMCs after oxidative injury to endothelium.


Subject(s)
Calcium Channels/metabolism , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Endothelium, Vascular/metabolism , Muscle, Smooth, Vascular/physiology , Oxidative Stress/physiology , Proliferating Cell Nuclear Antigen/genetics , Animals , Benzylamines/administration & dosage , Blood-Brain Barrier/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Cyclic AMP Response Element-Binding Protein/metabolism , Gene Expression Regulation , Phosphorylation , Posterior Cerebral Artery , Rats , Sulfonamides/administration & dosage , Superoxide Dismutase/metabolism , Superoxide Dismutase-1 , Transcriptional Activation , Triflupromazine/administration & dosage , Up-Regulation
3.
J Control Release ; 68(3): 313-33, 2000 Sep 03.
Article in English | MEDLINE | ID: mdl-10974386

ABSTRACT

NMR imaging has been used to study the release behavior of two model drugs, triflupromazine-HCl and 5-fluorouracil, from swelling hydroxypropylmethylcellulose (HPMC) tablets. Preliminary experiments were performed on equilibrium mixtures of drug, polymer and water to determine how properties such as NMR relaxation parameters and self-diffusion were affected by the drug and polymer concentrations. The tablet swelling was restricted to one dimension and distributions of the water and model drugs were obtained by 1H and 19F imaging, respectively. The HPMC distribution at each time in the swelling process was determined indirectly from its effect on the relaxation parameters of the water and the drugs. In the one-dimensional swelling tablet, distributions of drug and polymer were compared to determine what factors influenced the release of drug from the swelling tablet. The distributions for triflupromazine-HCl and HPMC paralleled each other and the drug was only released at the eroding edge of the tablet where the HPMC concentration dropped below 10%. In contrast, 5-fluorouracil was released much more rapidly from the tablet and appeared to escape by diffusion from regions as high as 30% HPMC. An empirical measure of the rate of tablet edge movement can be obtained from plots of the edge position as a function of the square root of time. For HPMC, the rate of tablet expansion was determined in this way to be (2.4+/-0.8)x10(-6) cm(2) s(-1). The self-diffusion of triflupromazine-HCl in equilibrated mixtures of similar composition to the eroding tablet edge is approximately 3x10(-6) cm(2) s(-1) while the self-diffusion coefficient of 5-fluorouracil remained higher than this value until the HPMC concentration reached about 30%. This comparison of 'diffusion' properties may be useful in predicting the mechanism of drug release from other swelling hydrophilic matrix systems.


Subject(s)
Methylcellulose/analogs & derivatives , Pharmaceutical Preparations/administration & dosage , Calibration , Fluorouracil/administration & dosage , Hypromellose Derivatives , Magnetic Resonance Imaging , Methylcellulose/chemistry , Time Factors , Triflupromazine/administration & dosage
4.
Exp Mol Pathol ; 62(2): 75-82, 1995 Apr.
Article in English | MEDLINE | ID: mdl-8549698

ABSTRACT

Trifluopromazine (TFPro) administration to rats (50 mg/kg, ip) 30 min before or 6 or 10 hr after CCl4 treatment (1 ml/kg ip in olive oil) partially prevented necrogenic effects of this compound at 24 hr. TFPro has only minor effects on the covalent binding (CB) of CCl4-reactive metabolites to cellular constituents and even an enhancing action on CCl4-promoted lipid peroxidation (LP). Determination of TFPro levels in liver 1 and 3 hr after administration by gas chromatography/mass spectrometry showed its presence in that tissue at concentrations well above those needed for calmodulin (CaM) inhibitory effects of this drug. TFPro lowered body temperature in CCl4-treated animals during the 24-hr observation period. Protective effects of TFPro at 6 or 10 hr, when most of the CB and all of the LP has already occurred, suggest but do not prove a role for CaM in late stages of CCl4-induced necrogenic effects. Decreases in the body temperature of CCl4-poisoned animals provoked by TFPro might also play a role in the preventive actions of this drug.


Subject(s)
Carbon Tetrachloride Poisoning/prevention & control , Liver/pathology , Triflupromazine/pharmacology , Animals , Body Temperature/drug effects , Calmodulin/antagonists & inhibitors , Injections, Intraperitoneal , Lipid Peroxidation/drug effects , Liver/drug effects , Male , Microsomes, Liver/metabolism , Necrosis/chemically induced , Necrosis/prevention & control , Rats , Rats, Sprague-Dawley , Triflupromazine/administration & dosage , Triflupromazine/metabolism
5.
Z Geburtshilfe Perinatol ; 196(2): 78-82, 1992.
Article in German | MEDLINE | ID: mdl-1609533

ABSTRACT

The aim of this prospective, randomised, blind study was to investigate the analgesic potency and tolerance of intramuscular Tramadol compared to a standard obstetric analgesia with Pethidine. Triflupromazine was administrated in combination with the two tested analgesics in order to study its efficacy in alleviating the emetic side effects of the tested analgesics. 66 parturients were randomly assigned to three groups: group A: 100 mg Tramadol (Tramal), group B: 100 mg Tramadol (Tramal) and 10 mg Triflupromazine (Psyquil), group C: 50 mg Pethidine (Alodan) and 10 mg Triflupromazine (Psyquil). No significant differences concerning duration of labour, FHR-alterations, umbilical cord blood gases, respiration pattern and Apgar Scores of the neonate occurred. In all three groups the analgesic effect was equally good. Combination of the analgesic with the antiemetic showed no reduction of the incidence and severity of side effects.


Subject(s)
Analgesia, Obstetrical/methods , Meperidine/administration & dosage , Tramadol/administration & dosage , Triflupromazine/administration & dosage , Adult , Cardiotocography/drug effects , Dose-Response Relationship, Drug , Female , Humans , Infant, Newborn , Injections, Intramuscular , Meperidine/adverse effects , Oxytocin/administration & dosage , Pain Measurement , Pregnancy , Prospective Studies , Tramadol/adverse effects , Triflupromazine/adverse effects , Uterine Contraction/drug effects
9.
Article in English | MEDLINE | ID: mdl-1233526

ABSTRACT

There are many reasons why once a day oral dosage may be advantageous in administration of psychotropic drugs to mental patients, such as convenience for the patient, avoided side effects, ease of remembering, all of which contribute to reliable dosage as well as cost savings. This paper illustrates cost data, pharmacokinetics of psychotropic drugs, and suggests a basis for determining adequate pill size for unit dosage. On a cost per milligram basis, there is economic savings if medication is prescribed in the largest size the patient can conveniently take. Pharmacological data support a rationale for higher unit dosage. They indicate a dose response relationship between dose and therapeutic effectiveness and probably a blood level relationship. The long half-life indicates that once-a-day medication is a reasonable dosage schedule. The most important evidence for once-a-day medication, however, is the empirical evidence that it works, and is safe. Dosage information from double blind investigations provides a basis for determining adequacy of pill size for antipsychotic therapy.


Subject(s)
Drug Prescriptions , Psychotropic Drugs/administration & dosage , Chicago , Chlorpromazine/administration & dosage , Chlorprothixene/administration & dosage , Costs and Cost Analysis , Dose-Response Relationship, Drug , Haloperidol/administration & dosage , Humans , Psychotropic Drugs/metabolism , Thioridazine/administration & dosage , Triflupromazine/administration & dosage
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