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Zhurnal Nevrologii I Psikhiatrii Imeni... 2015to study the efficacy of the GABA-ergic drug pantogam active (D-, L-gopantenic acid) in patients with schizophrenia treated with typical neuroleptics and to assess the... (Comparative Study)
Comparative Study
OBJECTIVE
to study the efficacy of the GABA-ergic drug pantogam active (D-, L-gopantenic acid) in patients with schizophrenia treated with typical neuroleptics and to assess the rate of treatment response and tolerability of the drug.
MATERIAL AND METHODS
A sample consisted of 70 patients with schizophrenia stratified into main (n=35) and control (n=35) groups. All patients received one of typical antipsychotics (haloperidol, zuclopenthixol, promazine or perphenazine). Patients of the main group received in addition pantogam active in dose of 1200-1800 mg daily. The maximum allowed dose of 1800 mg daily was used in 62.9% of the patients.
RESULTS AND CONCLUSION
The long-term combined therapy with the addition of D-, L-gopantenic acid (pantogam activ) allowed to achieve clinical improvement earlier (on 8th week in the main group versus 16th week in the control group). The frequency and severity of secondary negative symptoms associated with antipsychotic therapy were decreased as well. The high efficacy and tolerability of the combined therapy allow to improve quality of life in patients with schizophrenia and their compliance to treatment as well as to reduce costs of medical care.
Topics: Adult; Antipsychotic Agents; Cognition; Female; GABA Agents; Humans; Male; Pantothenic Acid; Quality of Life; Schizophrenia; Treatment Outcome; gamma-Aminobutyric Acid
PubMed: 26356612
DOI: 10.17116/jnevro20151158128-34 -
European Journal of Mass Spectrometry... 2015The application of electrospray ionization (ESI) ion mobility (IM) spectrometry on the detection end of a high-performance liquid chromatograph has been a subject of...
The application of electrospray ionization (ESI) ion mobility (IM) spectrometry on the detection end of a high-performance liquid chromatograph has been a subject of study for some time. So far, this method has been limited to low flow rates or has required splitting of the liquid flow. This work presents a novel concept of an ESI source facilitating the stable operation of the spectrometer at flow rates between 10 μL mn(-1) and 1500 μL min(-1) without flow splitting, advancing the T-cylinder design developed by Kurnin and co-workers. Flow rates eight times faster than previously reported were achieved because of a more efficient dispersion of the liquid at increased electrospray voltages combined with nebulization by a sheath gas. Imaging revealed the spray operation to be in a rotationally symmetric multijet mode. The novel ESI-IM spectrometer tolerates high water contents (≤90%) and electrolyte concentrations up to 10mM, meeting another condition required of high-performance liquid chromatography (HPLC) detectors. Limits of detection of 50 nM for promazine in the positive mode and 1 μM for 1,3-dinitrobenzene in the negative mode were established. Three mixtures of reduced complexity (five surfactants, four neuroleptics, and two isomers) were separated in the millisecond regime in stand-alone operation of the spectrometer. Separations of two more complex mixtures (five neuroleptics and 13 pesticides) demonstrate the application of the spectrometer as an HPLC detector. The examples illustrate the advantages of the spectrometer over the established diode array detector, in terms of additional IM separation of substances not fully separated in the retention time domain as well as identification of substances based on their characteristic Ims.
PubMed: 26307720
DOI: 10.1255/ejms.1367 -
CNS Drugs Jul 2015To investigate the association between antipsychotic drug use and the development of first-time seizures in patients with schizophrenia, affective disorders, or dementia.
OBJECTIVE
To investigate the association between antipsychotic drug use and the development of first-time seizures in patients with schizophrenia, affective disorders, or dementia.
METHODS
We used data from the UK-based Clinical Practice Research Datalink database to conduct a follow-up study with a nested case-control analysis between 1998 and 2013. We identified patients with schizophrenia, affective disorders, or dementia, and estimated incidence rates of seizures among users of four antipsychotic drug subclasses, defined according to existing hypotheses on their seizure-inducing potential (1, olanzapine or quetiapine; 2, amisulpride, aripiprazole, risperidone, or sulpiride; 3, low-to-medium potency first-generation antipsychotic drugs [chlorpromazine, zuclopenthixol, flupenthixol, pericyazine, promazine, thioridazine]; 4, medium-to-high potency first-generation antipsychotic drugs [haloperidol, prochlorperazine, trifluoperazine]), and among those who did not use antipsychotic drugs. To adjust for confounding, we estimated odds ratios for seizures separately among patients with affective disorders or dementia, stratified by antipsychotic drug use and timing of use.
RESULTS
In the total cohort of 60,121 patients (who had schizophrenia, affective disorders, or dementia), the incidence rate of seizures per 10,000 person-years was 32.6 (95 % confidence interval [CI] 22.6-42.6) in users of olanzapine or quetiapine, 24.1 (95 % CI 13.2-34.9) in users of amisulpride, aripiprazole, risperidone, or sulpiride, 49.4 (95 % CI 27.7-71.0) in users of low-to-medium potency antipsychotic drugs, 59.1 (95 % CI 40.1-78.2) in users of medium-to-high potency antipsychotic drugs, and 11.7 (95 % CI 10.0-13.4) in non-users of antipsychotic drugs. Patients with dementia had significantly higher incidence rates of first-time seizures compared with patients with affective disorders, irrespective of antipsychotic drug use. In patients with affective disorders, current use of medium-to-high potency first-generation antipsychotic drugs was associated with an increased risk of seizures (adjusted odds ratio 2.51 [95 % CI 1.51-4.18]) compared with non-use, while use of other antipsychotic drugs was not associated with seizures. In patients with dementia, current use of olanzapine or quetiapine (adjusted odds ratio 2.37 [95 % CI 1.35-4.15]), low-to-medium potency first-generation antipsychotic drugs (adjusted odds ratio 3.08 [95 % CI 1.34-7.08]), and medium-to-high potency first-generation antipsychotic drugs (adjusted odds ratio 2.24 [95 % CI 1.05-4.81]) was associated with an increased risk of seizures compared with non-use, but current use of amisulpride, aripiprazole, risperidone, or sulpiride (adjusted odds ratio 0.92 [95 % CI 0.48-1.75]) was not. Use of antipsychotic drugs in patients with schizophrenia could not be investigated because of small numbers.
CONCLUSIONS
Current use of medium-to-high potency first-generation antipsychotic drugs was associated with a 2.5-fold increased risk of seizures compared with non-use of antipsychotic drugs in patients with affective disorders. In these patients, current use of all other antipsychotic drug subclasses was not associated with seizures. In patients with dementia, current and past use of all antipsychotic drug subclasses, except amisulpride, aripiprazole, risperidone, or sulpiride, was associated with an increased risk of seizures.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Case-Control Studies; Databases, Factual; Dementia; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Mood Disorders; Odds Ratio; Retrospective Studies; Risk; Schizophrenia; Seizures; United Kingdom; Young Adult
PubMed: 26242478
DOI: 10.1007/s40263-015-0262-y -
Journal of Clinical and Translational... Jul 2015A reduction in body temperature can be achieved by a downward adjustment of the termoneutral zone, a process also described as anapyrexia. Pharmacological induction of... (Review)
Review
A reduction in body temperature can be achieved by a downward adjustment of the termoneutral zone, a process also described as anapyrexia. Pharmacological induction of anapyrexia could enable numerous applications in medicine. However, little is known about the potential of pharmacological agents to induce anapyrexic signaling. Therefore, a review of literature was performed and over a thousand pharmacologically active compounds were analyzed for their ability to induce anapyrexia in animals. Based on this analysis, eight agents (helium, dimethyl sulfoxide, reserpine, (oxo)tremorine, pentobarbital, (chlor) promazine, insulin, and acetaminophen) were identified as potential anapyrexia-inducing compounds and discussed in detail. The translational pitfalls were also addressed for each candidate compound. Of the agents that were discussed, reserpine, (oxo)tremorine, and (chlor) promazine may possess true anapyrexic properties based on their ability to either affect the thermoneutral zone or its effectors and facilitate hypothermic signaling. However, these properties are currently not unequivocal and warrant further examination in the context of artificially-induced hypometabolism.
PubMed: 30873441
DOI: No ID Found -
Colloids and Surfaces. B, Biointerfaces Jan 2016Phenothiazine derivatives are non-antibiotics with antimicrobial, fungistatic and fungicidal effects. We exposed to a high energy UV laser beam phenothiazines solutions...
Phenothiazine derivatives are non-antibiotics with antimicrobial, fungistatic and fungicidal effects. We exposed to a high energy UV laser beam phenothiazines solutions in water at 20mg/mL concentration to increase antibacterial activity of resulting mixtures. Compared to previous results obtained on bacteria, more research is needed about UV laser irradiated phenothiazines applications on cancer cell cultures to evidence possible anticancerous properties. Evaluation of the safety of the newly obtained photoproducts in view of use on humans is also needed. Due to expensive animal testing in toxicology and pressure from general public and governments to develop alternatives to in vivo testing, in vitro cell-based models are attractive for preliminary testing of new materials. Cytotoxicity screening reported here shows that laser irradiated (4h exposure time length) chlorpromazine and promazine are more efficient against some cell cultures. Interaction of laser irradiated phenothiazines with fabrics show that promethazine and chlorpromazine have improved wetting properties. Correlation of these two groups of properties shows that chlorpromazine appears to be more recommended for applications on tissues using fabrics as transport vectors. The reported results concern stability study of phenothiazines water solutions to know the time limits within which they are stable and may be used.
Topics: 3T3 Cells; Animals; Erythrocytes; Hemolysis; Humans; Lasers; Mice; Phenothiazines; Textiles
PubMed: 26187648
DOI: 10.1016/j.colsurfb.2015.06.041 -
Free Radical Biology & Medicine Sep 2015NADPH oxidases (NOXs) constitute a family of enzymes generating reactive oxygen species (ROS) and are increasingly recognized as interesting drug targets. Here we...
NADPH oxidases (NOXs) constitute a family of enzymes generating reactive oxygen species (ROS) and are increasingly recognized as interesting drug targets. Here we investigated the effects of 10 phenothiazine compounds on NOX activity using an extensive panel of assays to measure production of ROS (Amplex red, WST-1, MCLA) and oxygen consumption. Striking differences between highly similar phenothiazines were observed. Two phenothiazines without N-substitution, including ML171, did not inhibit NOX enzymes, but showed assay interference. Introduction of an aliphatic amine chain on the N atom of the phenothiazine B ring (promazine) conferred inhibitory activity toward NOX2, NOX4, and NOX5 but not NOX1 and NOX3. Addition of an electron-attracting substituent in position 2 of the C ring extended the inhibitory activity to NOX1 and NOX3, with thioridazine being the most potent inhibitor. In contrast, the presence of a methylsulfoxide group at the same position (mesoridazine) entirely abolished NOX-inhibitory activity. A cell-free NOX2 assay suggested that inhibition by N-substituted phenothiazines was not due to competition with NADPH. A functional implication of NOX-inhibitory activity of thioridazine was demonstrated by its ability to block redox-dependent myofibroblast differentiation. Our results demonstrate that NOX-inhibitory activity is not a common feature of all antipsychotic phenothiazines and that substitution on the B-ring nitrogen is crucial for the activity, whereas that on the second position of the C ring modulates it. Our findings contribute to a better understanding of NOX pharmacology and might pave the path to discovery of more potent and selective NOX inhibitors.
Topics: Animals; CHO Cells; Cell Differentiation; Cricetinae; Cricetulus; Drug Evaluation, Preclinical; Enzyme Inhibitors; HEK293 Cells; Humans; Inhibitory Concentration 50; Myofibroblasts; NADPH Oxidases; Oxidation-Reduction; Oxidative Stress; Oxygen Consumption; Phenothiazines; Reactive Oxygen Species; Structure-Activity Relationship
PubMed: 26013584
DOI: 10.1016/j.freeradbiomed.2015.05.023 -
Analytical Chemistry Feb 2015The effects of medicine on the biomolecular interaction have been given increasing attention in biochemistry and affinity-based analytics since the environment in vivo...
The effects of medicine on the biomolecular interaction have been given increasing attention in biochemistry and affinity-based analytics since the environment in vivo is complex especially for the patients. Herein, myoglobin, a biomarker of acute myocardial infarction, was used as a model, and the medicine effects on the interactions of myoglobin/aptamer and myoglobin/antibody were systematically investigated using atomic force microscopy (AFM) for the first time. The results showed that the average binding force and the binding probability of myoglobin/aptamer almost remained unchanged after myoglobin-modified gold substrate was incubated with promazine, amoxicillin, aspirin, and sodium penicillin, respectively. These parameters were changed for myoglobin/antibody after the myoglobin-modified gold substrate was treated with these medicines. For promazine and amoxicillin, they resulted in the change of binding force distribution of myoglobin/antibody (i.e., from unimodal distribution to bimodal distribution) and the increase of binding probability; for aspirin, it only resulted in the change of the binding force distribution, and for sodium penicillin, it resulted in the increase of the average binding force and the binding probability. These results may be attributed to the different interaction modes and binding sites between myoglobin/aptamer and myoglobin/antibody, the different structures between aptamer and antibody, and the effects of medicines on the conformations of myoglobin. These findings could enrich our understanding of medicine effects on the interactions of aptamer and antibody to their target proteins. Moreover, this work will lay a good foundation for better research and extensive applications of biomolecular interaction, especially in the design of biosensors in complex systems.
Topics: Amoxicillin; Antibodies; Aptamers, Nucleotide; Aspirin; Binding Sites; Biomarkers; Gold; Microscopy, Atomic Force; Myoglobin; Penicillin G; Promazine; Protein Binding
PubMed: 25615803
DOI: 10.1021/ac503885e -
International Journal of Cardiology Nov 2014
Topics: Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Dementia; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Female; Heart Ventricles; Humans; Promazine; Propafenone; Torsades de Pointes; Ventricular Function, Left
PubMed: 25499340
DOI: 10.1016/j.ijcard.2014.09.095 -
International Journal of Pharmaceutics Nov 2014Phenothiazine drugs - chlorpromazine (CPZ), promazine (PZ) and promethazine (PMZ) - were exposed to 266 nm (fourth harmonic of the Nd:YAG pulsed laser radiation) in...
Phenothiazine drugs - chlorpromazine (CPZ), promazine (PZ) and promethazine (PMZ) - were exposed to 266 nm (fourth harmonic of the Nd:YAG pulsed laser radiation) in order to be modified at molecular level and to produce an enhancement of their antibacterial activity. The irradiated samples were analysed by several methods: pH and surface tension measurements, UV-vis-NIR absorption spectroscopy, laser induced fluorescence and thin layer chromatography. The purpose of these investigations was to study and describe the modified properties of the medicines to further investigate their specific interactions with materials such as cotton, polyester and Parafilm M as a model smooth surface. The textile materials may be impregnated with phenothiazines drug solutions exposed to laser radiation in order to be used in treatments applied on the surface of the organism. Some of the phenothiazines solutions exposed prolonged time intervals to laser radiation have much better activity against several bacteria. Therefore, in the paper, it is reported the wetting behaviour of CPZ, PZ and PMZ solutions, irradiated for time intervals between 1 and 240 min, on the surfaces of the three textures in order to draw a conclusion about their wettability as a function of time.
Topics: Anti-Bacterial Agents; Chlorpromazine; Chromatography, Thin Layer; Cotton Fiber; Hydrogen-Ion Concentration; Lasers; Paraffin; Phenothiazines; Polyesters; Promazine; Promethazine; Solutions; Surface Tension; Wettability
PubMed: 25148730
DOI: 10.1016/j.ijpharm.2014.08.031 -
Medicinski Glasnik : Official... Aug 2014To investigate the incidence of dyslipidemia (hypertriglyceridemia and hypercholesterolemia) in patients treated with antipsychotics of new generation compared to...
The incidence of dyslipidemia (hypertriglyceridemia and hypercholesterolemia) in patients treated with the new generation of antipsychotic drugs compared to conventional therapy.
AIM
To investigate the incidence of dyslipidemia (hypertriglyceridemia and hypercholesterolemia) in patients treated with antipsychotics of new generation compared to conventional therapy.
METHODS
This retrospective study included 116 chronic psychiatric patients divided into two groups: a test group who were on treatment with antipsychotics of the new generation and a control group who were treated with classical antipsychotics. Laboratory and vital parameters were monitored in a group of patients who were treated with new generation antipsychotics (clozapine, olanzapine, risperidone), as well as in the group of patients who were treated with classical antipsychotics (promazine, levopromazin,haloperidol, fluphenazine).
RESULTS
Mean triglyceride level in the test group was 3.13 mmol/L, and for the control group, 2.28 mmol/L, while the mean value for cholesterol test group was 6.12 mmol/L, and for the control group, 5.85 mmol/L. The average age of the test group was 49.6 years, while the control group was 51.47 years. There was a statistical significance in triglycerides (p = 0.004), while the cholesterol (p = 0.239) and age (p = 0.356) had no statistical significance in the test group compared to the patients who were treated by the new generation of antipsychotics, and the control group of patients who were treated with antipsychotics.
CONCLUSION
Dyslipidemia in the form of hypertriglyceridemia occurs more frequently in patients on therapy with the new generation of antipsychotics compared to patients treated with conventional therapy. Hypercholesterolemia as a form of dyslipidemia had not been proven as significantly frequent during the therapy with new antipsychotics in relation to classical antipsychotic treatment.
Topics: Adult; Aged; Antipsychotic Agents; Bosnia and Herzegovina; Dyslipidemias; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Incidence; Male; Middle Aged; Retrospective Studies
PubMed: 25082252
DOI: No ID Found