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Clinical Neurophysiology : Official... Dec 2014Limited information is available regarding sedation and motor function following repeat dosing of antihistamines. This study examined how promethazine and loratadine... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Limited information is available regarding sedation and motor function following repeat dosing of antihistamines. This study examined how promethazine and loratadine affect day-time drowsiness, the commencement of voluntary movement, and involuntary movement when administered on consecutive days.
METHODS
Ten healthy young subjects (24±5years) were recruited into a double-blind, placebo-controlled, three-way crossover study. Subjects ingested either promethazine, loratadine or a placebo, and ingested the same drug 24h later. Measures of drowsiness, simple reaction time (SRT), choice reaction time (CRT), and postural tremor were obtained pre-ingestion, 1h post-ingestion and 2h post-ingestion on each day.
RESULTS
Consecutive daily doses of promethazine and loratadine affected SRT and CRT, respectively, whereby reaction time deficits were less pronounced following the repeat dose. A reduced tremor response was also observed following consecutive daily dosing of promethazine, in contrast to loratadine which caused an increase in tremor amplitude with the consecutive daily dose.
CONCLUSIONS
Reaction time and tremor responses differed following the single dose compared to consecutive doses.
SIGNIFICANCE
Sufferers of allergic rhinitis often require antihistamine dosing regimens that continue over multiple days. Future studies will benefit from examining drowsiness and movement responses following single doses as well as consecutive dosing.
Topics: Adult; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Histamine H1 Antagonists; Humans; Loratadine; Male; Promethazine; Reaction Time; Sleep Stages; Tremor; Young Adult
PubMed: 24791618
DOI: 10.1016/j.clinph.2014.03.026 -
Brain Research Jul 2021After ischemic stroke, the increased catabolism of glucose (hyperglycolysis) results in the production of reactive oxygen species (ROS) via nicotinamide adenine...
BACKGROUND
After ischemic stroke, the increased catabolism of glucose (hyperglycolysis) results in the production of reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). A depressive or hibernation-like effect of C + P on brain activity was reported to induce neuroprotection. The current study assesses the effect of C + P on hyperglycolysis and NOX activation.
METHODS
Adult male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by 6 or 24 h of reperfusion. At the onset of reperfusion, rats received C + P with or without temperature control, or phloretin [glucose transporter (GLUT)-1 inhibitor], or cytochalasin B (GLUT-3 inhibitor). We detected brain ROS, apoptotic cell death, and ATP levels along with HIF-1α expression. Cerebral hyperglycolysis was measured by glucose, protein expression of GLUT-1/3, and phosphofructokinase-1 (PFK-1), as well as lactate and lactate dehydrogenase (LDH) at 6 and 24 h of reperfusion. The enzymatic activity of NOX and protein expression of its subunits (gp91) were detected. Neural SHSY5Y cells were placed under 2 h of oxygen-glucose deprivation (OGD) followed by reoxygenation for 6 and 24 h with C + P treatment. Cell viability and protein levels of HIF-1α, GLUT-1/3, PFK-1, LDH, and gp91 were measured. A HIF-1α overexpression vector was transfected into the cells, and then protein levels of HIF-1α, GLUT-1/3, PFK-1, and LDH were quantitated. In sham-operated rats and control cells, the protein levels of HIF-1α, GLUT-1/3, PFK-1, LDH, and gp91 were measured at 6 and 24 h after C + P administration.
RESULTS
C + P reduced the protein elevations after stroke in HIF-1α, glycolytic enzymes, as well as in ROS, cell death, glucose and lactate, but raised ATP levels in the brain. In ischemic rats exposed to GLUT-1/3 inhibitors, ROS, cell death, glucose, and lactate were all decreased, as well as GLUT-1, GLUT-3, LDH, and PFK-1 protein levels. C + P decreased ischemia-induced NOX activation by reducing the enzymatic activity and protein expression of the NOX subunit gp91, as was observed in the presence of GLUT-1/3 inhibitors. These markers were significantly decreased following C + P administration with the induced hypothermia, while C + P administration with temperature control at 37 °C induced lesser protection after ischemia stroke. In the OGD/reoxygenation model, C + P treatment increased cell viability and diminished protein levels of HIF-1α, GLUT-1, GLUT-3, PFK-1, LDH, and gp91. However, in OGD with HIF-1α overexpression, C + P was unable to effectively reduce the upregulated GLUT-1, GLUT-3, and LDH. In normal conditions, C + P reduced HIF-1α and the levels of key glycolytic enzymes depending on its pharmacological effect.
CONCLUSION
C + P, partially depending on hypothermia, attenuates hyperglycolysis and NOX activation through HIF-1α regulation.
Topics: Animals; Chlorpromazine; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 3; Glycolysis; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Infarction, Middle Cerebral Artery; Ischemic Stroke; L-Lactate Dehydrogenase; Male; NADPH Oxidase 2; Phosphofructokinase-1; Promethazine; Rats; Rats, Sprague-Dawley
PubMed: 33811844
DOI: 10.1016/j.brainres.2021.147463 -
Mediators of Inflammation 2022Cerebral ischemia-reperfusion (I/R) incites neurologic damage through a myriad of complex pathophysiological mechanisms, most notably, inflammation and oxidative stress....
Cerebral ischemia-reperfusion (I/R) incites neurologic damage through a myriad of complex pathophysiological mechanisms, most notably, inflammation and oxidative stress. In I/R injury, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) produces reactive oxygen species (ROS), which promote inflammatory and apoptotic pathways, augmenting ROS production and promoting cell death. Inhibiting ischemia-induced oxidative stress would be beneficial for reducing neuroinflammation and promoting neuronal cell survival. Studies have demonstrated that chlorpromazine and promethazine (C+P) induce neuroprotection. This study investigated how C+P minimizes oxidative stress triggered by ischemic injury. Adult male Sprague-Dawley rats were subject to middle cerebral artery occlusion (MCAO) and subsequent reperfusion. 8 mg/kg of C+P was injected into the rats when reperfusion was initiated. Neurologic damage was evaluated using infarct volumes, neurological deficit scoring, and TUNEL assays. NOX enzymatic activity, ROS production, protein expression of NOX subunits, manganese superoxide dismutase (MnSOD), and phosphorylation of PKC- were assessed. Neural SHSY5Y cells underwent oxygen-glucose deprivation (OGD) and subsequent reoxygenation and C+P treatment. We also evaluated ROS levels and NOX protein subunit expression, MnSOD, and p-PKC-/PKC-. Additionally, we measured PKC- membrane translocation and the level of interaction between NOX subunit (p47) and PKC- via coimmunoprecipitation. As hypothesized, treatment with C+P therapy decreased levels of neurologic damage. ROS production, NOX subunit expression, NOX activity, and p-PKC-/PKC- were all significantly decreased in subjects treated with C+P. C+P decreased membrane translocation of PKC- and lowered the level of interaction between p47 and PKC-. This study suggests that C+P induces neuroprotective effects in ischemic stroke through inhibiting oxidative stress. Our findings also indicate that PKC-, NOX, and MnSOD are vital regulators of oxidative processes, suggesting that C+P may serve as an antioxidant.
Topics: Animals; Brain Injuries; Brain Ischemia; Chlorpromazine; Ischemic Stroke; Male; NADPH Oxidases; Oxidative Stress; Promethazine; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Stroke; Superoxide Dismutase
PubMed: 35873710
DOI: 10.1155/2022/6886752 -
Frontiers in Neurology 2021Following an acute ischemic stroke (AIS), rapidly initiated reperfusion therapies [i. e., intravenous thrombolysis (IVT) and endovascular treatment (EVT)] demonstrate...
Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-Like Effect in Stroke: Rationale, Design, and Protocol for a Prospective Randomized Controlled Trial.
Following an acute ischemic stroke (AIS), rapidly initiated reperfusion therapies [i. e., intravenous thrombolysis (IVT) and endovascular treatment (EVT)] demonstrate robust clinical efficacy. However, only a subset of these patients can benefit from these therapies due to their short treatment windows and potential complications. In addition, many patients despite successful reperfusion still have unfavorable outcomes. Thus, neuroprotection strategies are urgently needed for AIS patients. Chlorpromazine and promethazine (C+P) have been employed in clinical practice for antipsychotic and sedative purposes. A clinical study has also shown a neuroprotective effect of C+P on patients with cerebral hemorrhage and subarachnoid hemorrhage. The safety, feasibility, and preliminary efficacy of intravenous administration of C+P in AIS patients within 24 h of onset will be elucidated. A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to an intervention group and a control group with a 1:1 ratio ( = 30) and will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the intervention group will receive intravenous administration of C+P (chlorpromazine 50 mg and promethazine 50 mg) within 24 h of symptom onset. The primary outcome is safety (mainly hypotension), while the secondary outcomes include changes in functional outcome and infarction volume. This study on Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-like Effect in Stroke (RICHES) will be the first prospective randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of intravenous C+P as a neuroprotection strategy in AIS patients. These results will provide parameters for future studies, provide insights into treatment effects, and neuroprotection with phenothiazine in AIS. www.chictr.org.cn, identifier: ChiCTR2000038727.
PubMed: 33815250
DOI: 10.3389/fneur.2021.621476 -
Biomedicine & Pharmacotherapy =... Nov 2021To elucidate the potential effect of promethazine on colorectal cancer (CRC) cells and the underlying mechanism.
AIM
To elucidate the potential effect of promethazine on colorectal cancer (CRC) cells and the underlying mechanism.
MATERIALS AND METHODS
Targets of the drug promethazine (PMTZ) were identified by DrugBank and comparative toxicogenomic databases (CTD), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed with STRING software. The effects of PMTZ were predicted to be associated with the PI3K/AKT pathway. Cell Counting Kit 8 (CCK-8) assays were used to evaluate the effects of different concentrations of PMTZ on the proliferation of various types of CRC cells. Flow cytometry and Western blotting analyses were used to detect the degree of CRC cell apoptosis and the expression of the apoptosis-related proteins Bcl-2, Bax and caspase-3 after PMTZ treatment. The expression levels of PI3K/AKT pathway-related proteins [PI3K, AKT, phosphorylated (P)-PI3K and p-AKT] in CRC cells treated with PMTZ were analyzed by Western blotting.
RESULTS
PMTZ inhibited the proliferation and promoted the apoptosis of CRC cells and suppressed the activation of the PI3K/AKT signaling pathway in a dose-dependent manner.
DISCUSSION AND CONCLUSIONS
PMTZ may suppress the proliferation and induce the apoptosis of CRC cells by inhibiting the PI3K/ AKT signaling pathway. This study reported, for the first time, the function of PMTZ in CRC cells and the underlying mechanism and further confirmed the potential antitumor effects of phenothiazine. The combination of bioinformatics analyses and experiments provides informative evidence for the reuse of drugs and the development of new drugs.
Topics: Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Caco-2 Cells; Cell Proliferation; Colorectal Neoplasms; Databases, Genetic; Drug Repositioning; Gene Expression Regulation, Neoplastic; HCT116 Cells; HT29 Cells; Humans; Mitochondria; Phosphatidylinositol 3-Kinase; Promethazine; Proto-Oncogene Proteins c-akt; Signal Transduction
PubMed: 34560542
DOI: 10.1016/j.biopha.2021.112174 -
Journal of Obstetrics and Gynaecology... Dec 2016Hyperemesis gravidarum is the third leading cause of hospitalization during pregnancy. 5-HT3-receptor antagonists are the most effective against chemotherapy-induced...
PURPOSE
Hyperemesis gravidarum is the third leading cause of hospitalization during pregnancy. 5-HT3-receptor antagonists are the most effective against chemotherapy-induced nausea and vomiting and radiation. This randomized study aimed to compare and evaluate the efficacies of granisetron and promethazine for controlling nausea and vomiting of pregnancy.
METHODS
The included patients were administered (oral and intravenous) granisetron and promethazine randomly. The patients were evaluated for nausea and vomiting by a senior gynecology resident blinded to designated drugs.
RESULTS
This study revealed that granisetron significantly decreased nausea and vomiting in pregnant women ( < 0.05). Greater patient satisfaction and lesser adverse drug reactions in women receiving granisetron observed in this study suggest that it can be introduced as a more effective and safer drug in comparison with promethazine.
CONCLUSIONS
Considering the prevalence of nausea and vomiting of pregnancy and hyperemesis gravidarum, we can state that it is a health-related problem with economic, social and psychological dimensions. All efforts especially simple outpatient strategies to reduce its severity will help the pregnant woman continue her pregnancy with more satisfaction.
PubMed: 27821979
DOI: 10.1007/s13224-015-0709-6 -
The Analyst Mar 2023The discovery of novel chiral selectors always fascinates us. This work describes the chiral separation performances of a new chiral selector (kasugamycin, KAS) in...
The discovery of novel chiral selectors always fascinates us. This work describes the chiral separation performances of a new chiral selector (kasugamycin, KAS) in capillary electrophoresis (CE) for six pairs of stereoisomers, including ephedrine and pseudoephedrine, quinine and quinidine, cinchonine and cinchonidine, and amlodipine, promethazine and ofloxacin enantiomers. Kasugamycin, an aminoglycoside antibiotic in agriculture, shows significant biological activity against rice blast with low toxicity. As it turns out, this new chiral selector possesses good CE compatibility and stereoselectivity towards model analytes. In this work, we systematically investigated several separation parameters including kasugamycin concentration, buffer pH, separation voltage and the composition of the buffer solution. A detailed discussion about the chiral recognition mechanism was made based on Statistical Product and Service Solution (SPSS) analysis, NMR experiments (1D and 2D) and molecular modeling. This is the first time that kasugamycin is utilized as a chiral selector in CE, and the development of new chiral selectors from agricultural or veterinary antibiotics deserves more attention.
Topics: Anti-Bacterial Agents; Aminoglycosides; Ofloxacin; Electrophoresis, Capillary; Stereoisomerism; Hydrogen-Ion Concentration
PubMed: 36853240
DOI: 10.1039/d2an01949c -
Seminars in Perinatology Dec 2014With 50-90% of pregnant women experiencing nausea and vomiting of pregnancy (NVP), the burden of illness can become quite significant if symptoms are under-treated... (Review)
Review
With 50-90% of pregnant women experiencing nausea and vomiting of pregnancy (NVP), the burden of illness can become quite significant if symptoms are under-treated and/or under-diagnosed, thus allowing for progression of the disease. The majority of these women will necessitate at least one visit with a provider to specifically address NVP, and up to 10% or greater will require pharmacotherapy after failure of conservative measures to adequately control symptoms. As a result, initiation of prompt and effective treatment in the outpatient setting is ideal. Once NVP is diagnosed and treatment is started, it is crucial to track symptoms in order to assess for a decrease in or resolution of symptoms as well as an escalation in symptoms requiring additional therapy. Of note, co-existing gastroesophageal reflux disease (GERD), Helicobacter pylori infection, and psychosocial factors may have a negative impact on the management of NVP. Ultimately, every woman has her own perception of disease severity and desire for treatment. It is critical that both the provider and patient be proactive in the diagnosis and management of NVP.
Topics: Ambulatory Care; Antiemetics; Diet Therapy; Doxylamine; Female; Fluid Therapy; Gastroesophageal Reflux; Histamine H1 Antagonists; Humans; Hyperemesis Gravidarum; Metoclopramide; Morning Sickness; Ondansetron; Pregnancy; Promethazine; Pyridoxine; Severity of Illness Index; Vitamin B Complex
PubMed: 25267280
DOI: 10.1053/j.semperi.2014.08.014 -
Dermatitis : Contact, Atopic,...Little is known about the common photoallergens in New Zealand, where ultraviolet exposure is particularly high. Availability of photopatch testing is limited because of...
BACKGROUND
Little is known about the common photoallergens in New Zealand, where ultraviolet exposure is particularly high. Availability of photopatch testing is limited because of it being performed in very few tertiary referral and contact dermatitis clinics.
OBJECTIVE
To review the photopatch testing experience in New Zealand.
METHOD
A retrospective review of all patients who underwent photopatch testing at a tertiary referral center in Auckland from 2008 to 2019 was performed.
RESULTS
Seventy patients had photopatch testing over the 12-year period. Of the 58 patients tested using the photoallergen series, 6 (10%) patients had a positive photopatch test reaction, of which 4 were to promethazine and 2 were to benzophenone-3. The most common postpatch diagnosis was endogenous dermatitis (54%), followed by allergic contact dermatitis (21%), photoallergic contact dermatitis (9%), and chronic actinic dermatitis (4%).
CONCLUSIONS
Both patch and photopatch testing are important investigations in patients with suspected photoallergic contact dermatitis. Promethazine and benzophenone-3 were the most frequent and only photoallergens in our population. Promethazine sensitization was via oral exposure, supporting a mechanism of systematized photoallergy to promethazine.
Topics: Adult; Aged; Benzophenones; Cohort Studies; Dermatitis; Dermatitis, Allergic Contact; Dermatitis, Photoallergic; Female; Humans; Male; Middle Aged; New Zealand; Patch Tests; Photosensitivity Disorders; Promethazine; Retrospective Studies; Tertiary Care Centers; Ultraviolet Rays
PubMed: 33449480
DOI: 10.1097/DER.0000000000000683