Meta-Analysis Review

Authors: Hosam E Matar, Muhammad Qutayba Almerie, Samer Makhoul...

BACKGROUND

Pericyazine is a 3-cyano-10 (3-4'-hydroxypiperidinopropyl) phenothiazine. It is overall pharmacologically similar with chlorpromazine, though particularly sedating. Dopamine receptor subtype analysis has not been performed for pericyazine, but the drug appears to induce greater noradrenergic than dopaminergic blockade. Compared to chlorpromazine, pericyazine reportedly has more potent antiemetic, antiserotonin, and anticholinergic activity.

OBJECTIVES

To evaluate the clinical effects and safety of pericyazine in comparison with placebo, typical and atypical antipsychotic agents and standard care for people with schizophrenia.

SEARCH METHODS

We searched the Cochrane Schizophrenia Group Trials Register (February 2013) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials.

SELECTION CRITERIA

All relevant randomised controlled trials focusing on pericyazine for schizophrenia and other types of schizophrenia-like psychoses (schizophreniform and schizoaffective disorders). We excluded quasi-randomised trials.

DATA COLLECTION AND ANALYSIS

Data were extracted independently from included papers by at least two review authors. Risk ratios (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data were calculated. We assessed risk of bias for included studies and used GRADE to judge quality of evidence.

MAIN RESULTS

We could only include five studies conducted between 1965 and 1980. Most of the included studies did not report details of randomisation, allocation concealment, details of blinding and we could not assess the impact of attrition due to poor reporting.For the primary outcome of Global state - not improved, the confidence interval was compatible with a small benefit and increased risk of not improving with pericyazine compared with typical antipsychotics (2 RCTs, n = 122, RR 1.24 CI 0.93 to 1.66, very low quality of evidence) or atypical antipsychotics (1 RCT, n = 93, RR 0.97 CI 0.67 to 1.42, very low quality of evidence).When compared with typical antipsychotics relapse was only experienced by one person taking pericyazine (1 RCT, n = 80, RR 2.59 CI 0.11 to 61.75, very low quality of evidence).Pericyazine was associated with more extrapyramidal side effects than typical antipsychotics (3 RCTs, n = 163, RR 0.52 CI 0.34 to 0.80, very low quality of evidence) and atypical antipsychotics (1 RCT, n = 93, RR 2.69 CI 1.35 to 5.36, very low quality of evidence).The estimated risk of leaving the study early for specific reasons was imprecise for the comparisons of pericyazine with typical antipsychotics (2 RCTs, n = 71, RR 0.46 CI 0.11 to 1.90, very low quality of evidence), and with atypical antipsychotics (1 RCT, n = 93, RR 0.13 CI 0.01 to 2.42, very low quality of evidence).

AUTHORS' CONCLUSIONS

On the basis of very low quality evidence we are unable to determine the effects of pericyazine in comparison with typical or atypical antipsychotics for the treatment of schizophrenia. However, there is some evidence that pericyazine may be associated with a higher incidence of extrapyramidal side effects than other antipsychotics, and again this was judged to be very low quality evidence. Large, robust studies are still needed before any firm conclusions can be drawn.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Humans; Phenothiazines; Randomized Controlled Trials as Topic; Schizophrenia; Spasm; Tremor

PubMed: 24825770
DOI: 10.1002/14651858.CD007479.pub2

Review

Authors: B Surawicz

Ventricular fibrillation is the most common mechanism of sudden unexpected cardiac death in persons with asymptomatic or symptomatic coronary artery disease. The electrophysiologic mechanisms reviewed in this article include: automaticity of pacemaker fibers, transformation of nonpacemaker into pacemaker fibers, "injury" currents and reentry. Some of the conditions facilitating ventricular fibrillation include bradycardia, long QT syndrome, electrocution, electrolyte imbalance, drugs, sympathetic stimulation and myocardial ischemia. Electrophysiologic studies during acute myocardial ischemia suggest that the earliest activity at the onset of arrhythmia may originate at the sites of the surviving Purkinje fibers or at the epicardial rim. Reentrant arrhythmias arising in ischemic myocardium are attributed to nonhomogeneous distribution of local hyperkalemia and acidosis.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Death, Sudden; Digitalis; Electric Stimulation; Electrocardiography; Electrophysiology; Heart Conduction System; Heart Rate; Heart Ventricles; Humans; Hypokalemia; Membrane Potentials; Pacemaker, Artificial; Phenothiazines; Plants, Medicinal; Plants, Toxic; Sympathetic Nervous System; Syndrome; Vagus Nerve; Ventricular Fibrillation

PubMed: 3889113
DOI: 10.1016/s0735-1097(85)80526-x

Review

Authors: Leonard Amaral, Miguel Viveiros, Joseph Molnar...

Multidrug-resistant Mycobacterium tuberculosis (MDRTB) and antibiotic-resistant Plasmodium falciparum are the major global lethal infections accounting for over 4 million deaths per year. Methicillin-resistant Staphylococcus aureus (MRSA) is the major global nosocomial infection and resistance to vancomycin is evident and may become common. This review provides the scientific and medical basis that support the use of one particular group of compounds, the phenothiazines, and in particular thioridazine, for the management of the above antibiotic-resistant infections. Because thioridazine, a relatively mild neuroleptic as compared to its parental compound chlorpromazine, kills intracellular MDRTB and MRSA at clinical concentrations, its use for the management of these infections may be considered. The review also discusses the activity of phenothiazines against protozoa and parasites, the mechanisms by which phenothiazines promote their antimicrobial effects, their potential for regulating efflux pumps that are a cause for mono or multidrug resistance, as well as their potential for the therapy of problematic infections caused by bacteria that have acquired plasmid-antibiotic-resistant genes.

Topics: Animals; Anti-Infective Agents; Drug Resistance; Humans; Phenothiazines; Thioridazine

PubMed: 15646813
DOI: No ID Found

Review

Authors: Genta Okude, Ryo Futahashi

The order Odonata (dragonflies and damselflies) comprises diurnal insects with well-developed vision, showing diverse colors in adult wings and bodies. It is one of the most ancestral winged insect groups. Because Odonata species use visual cues to recognize each other, color patterns have been investigated from ecological and evolutionary viewpoints. Here we review the recent progress on molecular mechanisms of pigmentation, especially focused on light-blue coloration. Results from histology and pigment analysis showed that ommochrome pigments on the proximal layer and pteridine pigments on the distal layer of the epidermis are essential for light-blue coloration. We also summarize genes involved in the biosynthesis of three major insect pigments conserved across insects and discuss that gene-functional analysis deserves future studies.

Topics: Animals; Color; Odonata; Phenothiazines; Phenotype; Pigmentation; Wings, Animal

PubMed: 33482606
DOI: 10.1016/j.gde.2020.12.014

Review

Authors: Agata Jaszczyszyn, Kazimierz Gąsiorowski, Piotr Świątek...

Phenothiazines belong to the oldest, synthetic antipsychotic drugs, which do not have their precursor in the world of natural compounds. Apart from their fundamental neuroleptic action connected with the dopaminergic receptors blockade, phenothiazine derivatives also exert diverse biological activities, which account for their cancer chemopreventive-effect, as: calmodulin- and protein kinase C inhibitory-actions, anti-proliferative effect, inhibition of P-glycoprotein transport function and reversion of multidrug resistance. According to literature data on relations between chemical structure of phenothiazines and their biological effects, the main directions for further chemical modifications have been established. They are provided and discussed in this review paper.

Topics: Antipsychotic Agents; Chemoprevention; Drug Resistance, Multiple; Phenothiazines; Structure-Activity Relationship

PubMed: 22580516
DOI: 10.1016/s1734-1140(12)70726-0

Authors: David B Kastrinsky, Jaya Sangodkar, Nilesh Zaware...

The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Humans; Mice; Neoplasms; Phenothiazines; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Transplantation, Heterologous; Vesicular Monoamine Transport Proteins

PubMed: 26372073
DOI: 10.1016/j.bmc.2015.07.007

Authors: Matthew Pittendreigh, Kaleigh Powers, Meenalosini Vimal Cruz...

The ommochrome and porphyrin body pigments that give freshwater planarians their brown color are produced by specialized dendritic cells located just beneath the epidermis. During embryonic development and regeneration, differentiation of new pigment cells gradually darkens newly formed tissue. Conversely, prolonged light exposure ablates pigment cells through a porphyrin-based mechanism similar to the one that causes light sensitivity in rare human disorders called porphyrias. Here, we describe a novel program using image-processing algorithms to quantify relative pigment levels in live animals and apply this program to analyze changes in bodily pigmentation induced by light exposure. This tool will facilitate further characterization of genetic pathways that affect pigment cell differentiation, ommochrome and porphyrin biosynthesis, and porphyrin-based photosensitivity.

Topics: Animals; Humans; Planarians; Pigmentation; Phenothiazines; Porphyrins

PubMed: 37428383
DOI: 10.1007/978-1-0716-3275-8_16

Authors: I Ray, W N Andrews

Topics: Antidepressive Agents; Canada; Community Mental Health Services; Depression; Fluphenazine; Humans; Methods; Motivation; Patient Care Team; Phenothiazines; Psychotherapy; Schizophrenia

PubMed: 5056113
DOI: No ID Found

Authors: Taizhen Liang, Shiqi Xiao, Ziyao Wu...

Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several US FDA-approved drugs and identified phenothiazine derivatives with the ability to potently inhibit the infection of pseudotyped SARS-CoV-2 and distinct variants of concern (VOCs), including B.1.617.2 (Delta) and currently circulating Omicron sublineages XBB and BQ.1.1, as well as pseudotyped SARS-CoV and MERS-CoV. Mechanistic studies suggested that phenothiazines predominantly inhibited SARS-CoV-2 pseudovirus (PsV) infection at the early stage and potentially bound to the spike (S) protein of SARS-CoV-2, which may prevent the proteolytic cleavage of the S protein, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that phenothiazines can serve as a potential broad-spectrum therapeutic drug for the treatment of SARS-CoV-2 infection as well as the infection of future emerging human coronaviruses (HCoVs).

Topics: Humans; SARS-CoV-2; Phenothiazines; COVID-19; Spike Glycoprotein, Coronavirus

PubMed: 37632009
DOI: 10.3390/v15081666

Authors: K Dawson-Butterworth

Topics: Blood Pressure; Chlorpromazine; Humans; Male; Phenothiazines; Priapism; Schizophrenia

PubMed: 5471763
DOI: 10.1136/bmj.4.5727.118-a