- Validation and Clinical Utility of the hERG IC50:CmaxRatio to Determine the Risk of Drug-Induced Torsades de Pointes: A Meta-Analysis. [Journal Article]
- PPharmacotherapy 2018 Jan 30
- CONCLUSIONS: The hERG IC50:Cmaxratio was correlated with TdP incidence for culprit drugs. This validation provides support for the potential use of the hERG IC50:Cmaxratio for clinical decision making in instances of drug selection where TdP risk is a concern.
- Sweet syndrome-like cutaneous drug reaction. [Case Reports]
- ABAn Bras Dermatol 2017 Nov-Dec; 92(6):858-860
- Cutaneous drug reactions are adverse reactions to medications that may present with different clinical features, ranging from localized to generalized lesions. In this report we describe a case of an...
Cutaneous drug reactions are adverse reactions to medications that may present with different clinical features, ranging from localized to generalized lesions. In this report we describe a case of an unusual drug reaction, resembling the morphology of Sweet syndrome lesions. The patient had a psychiatric illness and was using thioridazine hydrochloride for one year. He developed infiltrated and grouped erythematous lesions on the elbows and knees three days after commencing multiple drugs (promethazine, haloperidol, mirtazapine and levomepromazine). After suspension of these four drugs and after the use of glucocorticoids, the patient had significant clinical improvement.
- DR2 blocker thioridazine: A promising drug for ovarian cancer therapy. [Journal Article]
- OLOncol Lett 2017; 14(6):8171-8177
- Dopamine receptor 2 (DR2) may be a biomarker for various types of cancer. Ovarian cancer cells overexpress DR2; therefore, blocking DR2 may be a novel treatment strategy for ovarian cancer. Thioridaz...
Dopamine receptor 2 (DR2) may be a biomarker for various types of cancer. Ovarian cancer cells overexpress DR2; therefore, blocking DR2 may be a novel treatment strategy for ovarian cancer. Thioridazine, a DR2 blocker, has antineoplastic activity in a variety of cancer cells. In view of the requirement for novel therapeutic agents in ovarian cancer, the present study aimed to determine the potential effects of thioridazine in vitro and in vivo. It was revealed that the DR2 blocker thioridazine induced cell death in a dose-dependent manner in ovarian cancer cells. Thioridazine treatment induced apoptosis and autophagy, which may be attributed to an increased level of reactive oxygen species and associated DNA damage. Additionally, the expression of various proteins increased with oxidative stress, including nuclear factor E2-related factor 2, which is a pivotal transcriptional factor involved in cellular responses to oxidative stress. Heme oxygenase 1, NAPDH quinone dehydrogenase 1 and hypoxia inducible factor-1α and phosphorylated (p)-protein kinase B expression was significantly decreased, and the expression level of p-extracellular signal-related kinases and p-P38 was increased. Using 3-methyl adenine to inhibit autophagy caused the rate of apoptosis to increase. Thioridazine inhibited the growth of SKOV3 xenografts in nude mice. The present study demonstrated that the DR2 blocker thioridazine exhibited anticancer effects in vitro and in vivo, suggesting that thioridazine may be used as a potential drug in ovarian cancer therapy.
- Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity. [Journal Article]
- PlosPLoS One 2018; 13(1):e0189950
- Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described antipsychotic compounds that present anti...
Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described antipsychotic compounds that present antibacterial activity. Hence, the aims of this study were to evaluate the in vitro antibacterial activity of antipsychotics belonging to different chemical families, to assess the influence of their association with lipid nanocapsules (LNCs) on their antimicrobial activity as well as drug release and to study the uptake of LNCs by bacterial cells. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus and Gram negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by minimum inhibitory concentration (MIC) assay, and the capability of killing tested microorganisms was evaluated by time kill assay. LNCs were prepared by phase inversion method, and the antipsychotic agents were incorporated using pre-loading and post-loading strategies. Only phenothiazines and thioxanthenes showed antibacterial activity, which was independent of antibiotic-resistance patterns. Loading the nanocarriers with the drugs affected the properties of the former, particularly their zeta potential. The release rate depended on the drug and its concentration-a maximum of released drug of less than 40% over 24 hours was observed for promazine. The influence of the drug associations on the antibacterial properties was concentration-dependent since, at low concentrations (high nanocarrier/drug ratio), the activity was lost, probably due to the high affinity of the drug to nanocarriers and slow release rate, whereas at higher concentrations, the activity was well maintained for the majority of the drugs. Chlorpromazine and thioridazine increased the uptake of the LNCs by bacteria compared with blank LNCs, even below the minimum inhibitory concentration.
- Psychotropics and Male Reproduction. [Journal Article]
- AEAdv Exp Med Biol 2017; 1034:63-101
- Psychotropic drugs, including antidepressants, antipsychotics, and anticonvulsants, all have negative effects on sexual function and semen quality. These adverse events vary among men and are less pr...
Psychotropic drugs, including antidepressants, antipsychotics, and anticonvulsants, all have negative effects on sexual function and semen quality. These adverse events vary among men and are less pronounced for some medications, allowing their effects to be managed to some extent. Use of specific serotonin reuptake inhibitors (SSRIs) is prevalent in men of reproductive age; and application to treat premature ejaculation increases the number of young men on SSRI therapy. Oxidative damage to sperm can result from prolonged residence in the male reproductive tract. The increase in ejaculatory latency seen with SSRIs likely underlies some of their negative effects on semen quality, including higher sperm DNA fragmentation, seen in all SSRIs evaluated thus far. These medications increase prolactin (PRL) levels in some men, and this is often credited with inhibitory effects on male reproduction; however, testosterone levels are generally normal, reducing the likelihood of direct HPG axis inhibition by PRL. The tricyclic antidepressants have also been shown to increase PRL levels in some studies but not in others. The exception is the tricyclic antidepressant clomipramine, which profoundly increases PRL levels and may depress semen quality. Other antidepressants modulating synaptic levels of serotonin, norepinephrine, and/or dopamine may have toxicity similar to SSRIs, but most have not been evaluated. In limited studies, norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin agonist/reuptake inhibitors (SARIs) have had minimal effects on PRL levels and on sexual side effects. Antipsychotic medications increase PRL, decrease testosterone, and increase sexual side effects, including ejaculatory dysfunction. The greatest evidence is for chlorpromazine, haloperidol, reserpine, risperidone, and thioridazine, with less effects seen with aripiprazole and clozapine. Remarkably few studies have looked at antipsychotic effects on semen quality, and this is an important knowledge gap in reproductive pharmacology. Lithium increases PRL and LH levels and decreases testosterone although this is informed by few studies. The anticonvulsants, many used for other indications, generally decrease free or bioavailable testosterone with variable effects on the other reproductive hormones. Valproate, carbamazepine, oxcarbazepine, and levetiracetam decrease semen quality; other anticonvulsants have not been investigated for this adverse reaction. Studies are required evaluating endpoints of pregnancy and offspring health for psychotropic medications.
- [POISONING BY PSYCHOPHARMACOLOGICAL DRUGS IN AZERBAIJAN: THE RESULTS OF 8-YEAR PROSPECTIVE OBSERVATION]. [Journal Article]
- GMGeorgian Med News 2017; (272):138-144
- Acute poisoning of chemical etiology is a significant global public health problem. The aim of this study was the analysis of the toxicoepidemiological structure of psychopharmacological drugs poison...
Acute poisoning of chemical etiology is a significant global public health problem. The aim of this study was the analysis of the toxicoepidemiological structure of psychopharmacological drugs poisoning in Azerbaijan. We collected and analyzed the data on all cases of acute poisoning by psychopharmacological drugs (codes of categories T42/T43 ICD-10) undergoing inpatient treatment at the Center of Clinical Toxicology in Baku, Azerbaijan in 2009-2016. The total number of patients with acute intoxication by psychopharmacological drugs was 3,413, which was 48.3% of all cases of poisoning by drugs, medicaments and biological substances (T36-T50). The predominance of women was registered in all age groups. 1114 patients or 32.6% were in 15-24 years old age group. The highest percentage of poisonings at category T42 of ICD-10 were benzodiazepine-type drugs (35.8%), and at category T43 - antipsychotic and neuroleptic drugs (19.2%). In the structure of benzodiazepine poisoning, the first and second ranked places belonged to phenazepam (71.0%) and clonazepam - 16.6%. In addition, another 120 cases (5.5%) of poisonings in the T42 cohort were caused by "Z drugs", which have similar therapeutic effect to benzodiazepines (zolpidem and zopiclone). Among the antipsychotic and neuroleptic poisonings, thioridazine, trifluoperazine, levomepromazine, chlorpromazine, and periciazine accounted for 91% of all cases of intoxication in this cohort. Barbiturates, in view of their toxicity and narrow range of therapeutic dosages, now lost their importance as antiepileptic and hypnotic drugs. Only 4.9% of all cases of poisoning, classified under category T42, was due to the use of barbiturates (mainly phenobarbital). Poisonings with iminostilbenes were presented by carbamazepine poisoning only. Most patients in this cohort received this anticonvulsant drug as prescribed by a doctor. Acute intoxications by tricyclic antidepressants in 91.5% were presented by cases of amitriptyline poisoning. Intoxication by serotonin reuptake inhibitors antidepressants, were relatively rare (3.8% of all cases of poisoning in T43). Among the poisonings with butyrophenone and thioxanthene neuroleptics, the first ranked place was occupied by cases of haloperidol poisoning, which accounted for 82.6% in this cohort. In the group of intoxications with other antipsychotic and neuroleptic drugs, the first ranked place belonged to the poisoning with clozapine - a total of 83 cases or 47.2% in cohort. Poisonings by psychopharmacological drugs occupy the first ranking place among poisoning by drugs, medicaments and biological substances (T36-T50). Increased control over the prescription and sale of psychopharmacological drugs, a reduction the number of tablets in one package, as well as increased attention to vulnerable groups of the population could be help to reduce the percentage of these poisonings in Azerbaijan.
- Targeting TCTP with Sertraline and Thioridazine in Cancer Treatment. [Journal Article]
- RPResults Probl Cell Differ 2017; 64:283-290
- We have initially demonstrated in knocking down experiments that decreasing TCTP in cancer cells leads in some tissues to cell death while in others to a complete reorganization of the tumor into arc...
We have initially demonstrated in knocking down experiments that decreasing TCTP in cancer cells leads in some tissues to cell death while in others to a complete reorganization of the tumor into architectural structures reminiscent of normal ones. Based on these experiments and a series of other findings confirming the key role of TCTP in cancer, it became important to find pharmacological compounds to inhibit its function, and this became for us a priority. In the present text, we explain in detail the experiments that were performed and the perspectives of sertraline in cancer treatment, as this became today a reality with a clinical study that started in collaboration with Columbia University and Johns Hopkins University.
- Psychotropic agent thioridazine elicits potent in vitro and in vivo anti-melanoma effects. [Journal Article]
- BPBiomed Pharmacother 2018; 97:833-837
- Psychotropic agents have been shown anti-tumor potential in recent years. In the present study, our in vitro pharmacological data indicated that thioridazine inhibited melanoma cells proliferation. T...
Psychotropic agents have been shown anti-tumor potential in recent years. In the present study, our in vitro pharmacological data indicated that thioridazine inhibited melanoma cells proliferation. The growth-arresting effect of thioridazine was accompanied by autophagy induction, as shown by immunoblotting of increased LC3II. Besides, certain apoptotic events had also occurred after thioridazine exposure. The in vivo anti-melanoma effect of thioridazine was confirmed by showing that intraperitoneally injection of thioriazine remarkably retarded tumor growth and reduced tumor vasculature. Our results imply that thioridazine might be an available therapeutic agent for melanoma patients with no better options.
- Combining thioridazine and loratadine for the treatment of gastrointestinal tumor. [Journal Article]
- OLOncol Lett 2017; 14(4):4573-4580
- In 2015, the American Society of Clinical Oncology announced that strategies of using combination therapies have been indicated to be effective against many types of cancer. In the present study, thi...
In 2015, the American Society of Clinical Oncology announced that strategies of using combination therapies have been indicated to be effective against many types of cancer. In the present study, thioridazine (THZ) was used in a combination therapy with loratadine (LOR) to target gastrointestinal tumor, with the aim of investigating whether combined therapy was superior to monotherapy in its antitumor effects. The antiproliferative effects on CT26.WT and MFC cells were analyzed using cell-counting kit-8 assay, and synergistic effect was assessed by combination index (Fig. 1). Annexin V and propidium iodide staining indicated the combination therapy was able to induce apoptosis and that this may be mediated via caspase-3, -9 and poly (ADP-ribose) polymerase (PARP) (Fig. 2). Antitumor activity was also evaluated in CT26.WT xenografts in BALB/c mice (Fig. 3). Furthermore, as expected, combination therapy was able to successfully inhibit the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling pathway (Fig. 4). These findings suggest that the combination therapy with THZ and LOR may provide a promising therapy for gastrointestinal cancer.
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- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Similar to other first generation, or typical, antipsychotics, thioridazine is a medication used to treat schizophrenia. Other indications for use include other psychotic disorders, depressive disord...
Similar to other first generation, or typical, antipsychotics, thioridazine is a medication used to treat schizophrenia. Other indications for use include other psychotic disorders, depressive disorders, pediatric behavioral disorders, and geriatric psychoneurotic manifestations.