Search results for "Chlorpromazine"

Enhancement in Phospholipase D Activity as a New Proposed Molecular Mechanism of Haloperidol-Induced Neurotoxicity

2020

Membrane phospholipase D (PLD) is associated with numerous neuronal functions, such as axonal growth, synaptogenesis, formation of secretory vesicles, neurodegeneration, and apoptosis. PLD acts mainly on phosphatidylcholine, from which phosphatidic acid (PA) and choline are formed. In turn, PA is a key element of the PLD-dependent secondary messenger system. Changes in PLD activity are associated with the mechanism of action of olanzapine, an atypical antipsychotic. The aim of the present study was to assess the effect of short-term administration of the first-generation antipsychotic drugs haloperidol, chlorpromazine, and fluphenazine on membrane PLD activity in the rat brain. Animals were…

Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent.

2018

Abstract Cholestasis represents a major subtype of drug-induced liver injury and novel preclinical models for its prediction are needed. Here we used primary human hepatocytes (PHH) from different donors in 2D-sandwich (2D-sw) and/or 3D-spheroid cultures to study inter-individual differences in the response towards cholestatic hepatotoxins after short-term (48–72 hours) and long-term repeated exposures (14 days). The cholestatic liabilities of drugs were determined by comparing cell viability upon exposure to the highest non-cytotoxic drug concentration in the presence and absence of a non-cytotoxic concentrated bile acid mixture. In 2D-sw culture, cyclosporine A and amiodarone presented cl…

A Novel MicroRNA Signature for Cholestatic Drugs in Human Hepatocytes and Its Translation into Novel Circulating Biomarkers for Drug-Induced Liver In…

2019

AbstractDrug-induced liver injury (DILI) diagnosis and classification (hepatocellular, cholestatic, and mixed) relies on traditional clinical biomarkers (eg ALT and ALP), despite limitations such as extrahepatic interferences, narrow dynamic ranges, and low mechanistic value. microRNAs may be very useful for complementing traditional DILI biomarkers but most studies in this direction have considered only paracetamol poisoning. Thus the value of microRNAs (miRNAs) as biomarkers for idiosyncratic DILI has not yet been demonstrated. In this study, we first examined the effect of model cholestatic drugs on the human hepatocyte miRNome by RNAseq and RT-qPCR. Results demonstrated that chlorpromaz…

Two-year outcome in first-episode psychosis treated according to an integrated model. Is immediate neuroleptisation always needed?

2000

SummaryIn this multicentre study the two-year outcome of two groups of consecutive patients (total N = 106) with first-episode functional non-affective psychosis, both treated according to the ‘need-specific Finnish model’, which stresses teamwork, patient and family participation and basic psychotherapeutic attitudes, was compared. No alternative treatment facilities were available in the study sites. The two study groups differed in the use of neuroleptics: three of the sites (the experimental group) used a minimal neuroleptic regime whilst the other three (the control group) used neuroleptics according to the usual practice. Total time spent in hospital, occurrence of psychotic symptoms …

[123I]IBZM SPECT in patients treated with typical and atypical neuroleptics: relationship to drug plasma levels and extrapyramidal side effects

1997

[123I]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor ligand and can be used to visualize brain D2 receptors in humans with single photon emission computerized tomography (SPECT). The ratio of striatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D2 receptor binding in the striatum. Our study sample included six patients treated with haloperidol (3.0-8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscularly), five patients with benperidol (9.0-15.0 mg/day orally) and nine patients treated with clozapine (200.0-600.0 mg/day orally). Typical neuroleptics (TNs) and atypical neuroleptics (ANs) were significantly di…

Role of oxygen and nitrogen species in experimental uveitis: anti-inflammatory activity of the synthetic antioxidant ebselen.

2002

This study was aimed at examining the role of oxygen and nitrogen reactive species in a model of experimental uveitis upon intravitreal injection of bacterial endotoxin to albino New Zealand rabbits. The inflammatory response was evaluated in terms of: (i) the integrity of the blood aqueous barrier (protein and cell content in samples of aqueous humor), (ii) histopathological changes of the eyes, (iii) clinical evaluation (with a score index based on clinical symptoms), and (iv) the concentration of malondialdehyde (MDA), in aqueous humor, as a marker of oxidative stress. Betamethasone was used as reference treatment, superoxide dismutase as quencher of superoxide anion, L-N(G)-nitro-L-argi…

Albumin binding and hydrophobic character of promazine and chlorpromazine metabolites.

1972

1. The binding of didesmethylpromazine, promazine N-oxide, 2-hydroxypromazine, promazine sulfoxide, monodesmethylpromazine sulfoxide, didesmethylchlorpromazine, chlorpromazine N-oxide, and chlorpromazine sulfoxide to bovine serum albumin was determined by means of sephadex gel filtration. 2. The albumin binding of these substances was characterized by the following parameters: the percentage α of free substance, the percentage β of bound substance, the binding constants K1, k+ and m, the number of binding sites per albumin molecule, and the free binding energy ΔFo. 3. The partition coefficients between n-octanol and buffer solution, pH 7.40, were measured for the above mentioned metabolites…

Binding of several phenothiazine neuroleptics to a common binding site of alpha 1-acid glycoprotein, orosomucoid.

1983

The interaction of several phenothiazine neuroleptics with alpha 1-acid glycoprotein was investigated using circular dichroism and equilibrium dialysis techniques. For chlorpromazine only, one high-affinity binding site of the protein was found. The binding of the drug to this single site generated typical polyphasic extrinsic Cotton effects. Since several other phenothiazine neuroleptics gave qualitatively comparable extrinsic Cotton effects in the presence of alpha 1-acid glycoprotein and potently inhibited the binding of chlorpromazine to the single site, it was concluded that all phenothiazine derivatives investigated bound preferentially to only one common binding site of the alpha 1-a…

Entrapment of FePO4 in a polymeric matrix and their application to FIA-spectrophotometric determination of thioridazine and chlorpromazine in pharmac…

1998

Distribution of chlorpromazine in a simplified blood influenced by various drugs

1973

The binding of chlorpromazine to erythrocytes and to albumin as influenced by other drugs was studied in a simplified blood (31.5±0.3% bovine erythrocytes, 4 g-% bovine serum albumin in 0.02 M phosphate buffer solution containing 0.15 M NaCl). the total concentration of chlorpromazine in the simplified blood was 10−4 M, the concentration of the displacing drugs was 10−3 M. After an incubation period of 3 h at 22° C the chlorpromazine concentration was determined in the albumin solution after centrifugation of the blood at 3000×g and in the aqueous phase after ultracentrifugation at 150000×g. Under control conditions 68.1±0.9% of chlorpromazine was bound to the erythrocytes, 28.5±0.9% was bo…