Authors: Joanna Smajdor, Marcel Zambrzycki, Mateusz Marzec...

A new voltammetric method is proposed for high sensitive thiethylperazine (THP) determination, using a glassy carbon electrode modified with semi-graphitized carbon nanofibers/MnO nanocomposite (eCNF/MnO/GC). To the best of our knowledge, this is the first electrochemical assay of THP  determination, and the first use of the eCNF/MnO as the electrode modifier. The proposed method using eCNF/MnO/GC is characterized by high repeatability and sensitivity of measurements, with the linearity of THP in the range from 0.05 to 2.2 µmol L. The lowest detection limit achieved on the eCNF/MnO/GC electrode for 30 s of preconcentration was 6.3 nmol L THP in 0.05 mol L acetate buffer of  pH 5.6. The proposed method was successfully applied to highly sensitive THP determination in complex matrices, such as tablets and plasma with good recovery (98-103%). The RSD value obtained for THP measurement at a concentration of 0.1 µmol L was 1.3%. Amperometric measurements of THP under the flow injection conditions were also performed to indicate the possibility of its fast and accurate determination (103% and 95% for unmodified and modified electrode, respectively), with the duration of single analysis of approx. 30 s.

PubMed: 37874386
DOI: 10.1007/s00604-023-06025-1

Authors: Michael Wölfl-Duchek, Severin Mairinger, Irene Hernández-Lozano...

Multidrug resistance-associated protein 1 (MRP1, encoded by the gene) may contribute to the clearance of amyloid-beta (Aβ) peptides from the brain into the blood and stimulation of MRP1 transport activity may be a therapeutic approach to enhance brain Aβ clearance. In this study, we assessed the effect of thiethylperazine, an antiemetic drug which was shown to stimulate MRP1 activity in vitro and to decrease Aβ load in a rapid β-amyloidosis mouse model (APP/PS1-21), on MRP1 transport activity by means of positron emission tomography (PET) imaging with the MRP1 tracer 6-bromo-7-[C]methylpurine. Groups of wild-type, APP/PS1-21 and mice underwent PET scans before and after a 5-day oral treatment period with thiethylperazine (15 mg/kg, once daily). The elimination rate constant of radioactivity () was calculated from time-activity curves in the brain and the lungs as a measure of tissue MRP1 activity. Treatment with thiethylperazine had no significant effect on MRP1 activity in the brain and the lungs of wild-type and APP/PS1-21 mice. This may either be related to a lack of an MRP1-stimulating effect of thiethylperazine in vivo or to other factors, such as substrate-dependent MRP1 stimulation, insufficient target tissue exposure to thiethylperazine or limited sensitivity of the PET tracer to measure MRP1 stimulation.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Brain; Disease Models, Animal; Mice; Mice, Transgenic; Multidrug Resistance-Associated Proteins; Positron-Emission Tomography; Presenilin-1; Thiethylperazine

PubMed: 35742960
DOI: 10.3390/ijms23126514

Clinical Trial

Authors: G Wainscott, T Kaspi, G N Volans...

The absorption of effervescent aspirin was studied in three groups of patients during attacks of migraine. The first group received intramuscular thiethylperazine 10 min before effervescent aspirin; the second group received intramuscular metoclopramide 10 min before effervescent aspirin; and the third group received effervescent aspirin alone. Where possible each patient was retested when headache-free but under conditions which were otherwise as similar as possible to those during the acute attack. Intramuscular metoclopramide corrected the impairment of drug absorption that occurred during a migraine attack, whereas thiethylperazine did not. In the group of patients treated with thiethylperazine and aspirin, the impairment of absorption did not correlate with the duration of the symptoms, nor with the severity of the headache and nausea. Patients treated with thiethylperazine and aspirin tended to take longer to recover than those patients treated with metoclopramide and aspirin. However, in the thiethylperazine treated group, the time to recover did not correlate with the salicylate level achieved.

Topics: Adult; Antiemetics; Aspirin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Metoclopramide; Middle Aged; Migraine Disorders; Thiethylperazine

PubMed: 22216523
DOI: 10.1111/j.1365-2125.1976.tb00351.x

Review

Authors: M R Tramèr, D Carroll, F A Campbell...

OBJECTIVE

To quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy.

DESIGN

Systematic review.

DATA SOURCES

Systematic search (Medline, Embase, Cochrane library, bibliographies), any language, to August 2000.

STUDIES

30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours.

RESULTS

Cannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: "high" 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11.

CONCLUSIONS

In selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.

Topics: Antiemetics; Antineoplastic Agents; Cannabinoids; Humans; Nausea; Patient Satisfaction; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting

PubMed: 11440936
DOI: 10.1136/bmj.323.7303.16

Authors: Mohammad Rahbar, Hadi Mehrgan, Sanaz Hadji-nejad...

The antimicrobial and resistance-reversal activities of seven phenothiazine derivatives were evaluated against vancomycin-sensitive Enterococcus faecalis ATCC 29212, vancomycin resistant E. faecalis ATCC 51299 and ten vancomycin-resistant E. faecium strains originating from human infections. Minimum inhibitory concentrations (MIC) of the compounds were determined by agar dilution method, and synergy between phenothiazines and vancomycin was investigated using Checkerboard (microbroth dilution) technique. We found that all enterococci strains, regardless of their susceptibility to vancomycin, were inhibited by phenothiazines at concentrations varying from 8 to 256 microg/ml, with thiethylperazine being the most potent inhibitory agent. Besides, all the phenothiazines showed partial synergy with vancomycin and could lessen MIC of vancomycin from 512 to 8 microg/ml at their sub-inhibitory concentrations. The highest reduction in MIC was observed with chlorpromazine (32 times); however, thiethylperazine and promethazine stood next (24 times). Although resistance modification was observed at concentrations higher than those that phenothiazines reach in vivo, the potential offered by non-antibiotics justify further animal experiments as well as clinical trials to establish their clinical relevance.

Topics: Anti-Bacterial Agents; Drug Synergism; Drug Therapy, Combination; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Phenothiazines; Vancomycin; Vancomycin Resistance

PubMed: 20353486
DOI: 10.1111/j.1742-7843.2010.00558.x

Clinical Trial Randomized Controlled Trial

Authors: P M Plezia, D S Alberts, J F Kessler...

In a randomized open crossover study, the antiemetic efficacy of a five-drug antiemetic regimen consisting of metoclopramide, dexamethasone, diazepam, diphenhydramine, and thiethylperazine was compared to that of high-dose metoclopramide. Thirteen patients treated with cisplatin combination chemotherapy regimens were evaluated. The study was terminated prior to accrual of the planned number of patients because of the statistically significant difference in efficacy between treatments found at interim analysis. The duration of nausea and number of vomiting episodes on the day of chemotherapy were significantly less (p less than 0.01) after receiving the five-drug combination. After receiving the five-drug regimen, 77% of the patients did not experience any episodes of vomiting on day 1, and 8% of patients had only one episode. In contrast, only 31% of patients treated with high-dose metoclopramide did not have any episodes of vomiting on day 1, and 61% of the patients had five or more episodes. None of the patients treated with the five-drug regimen required additional antiemetic administration. Although both regimens were, in general, well tolerated, when given the choice of continuing antiemetic therapies, 92% of the patients preferred the five-drug antiemetic combination.

Topics: Adult; Aged; Cisplatin; Dexamethasone; Diazepam; Diphenhydramine; Drug Therapy, Combination; Humans; Metoclopramide; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Thiethylperazine; Vomiting

PubMed: 2189929
DOI: 10.1016/s0885-3924(05)80023-5

Authors: Agnieszka Kluczna, Elżbieta Mularska, Tomasz Dzierżanowski...

BACKGROUND

The SARS-CoV-2 pandemic has become a challenge for the entire healthcare system. Treatment for COVID-19 includes casual and symptomatic management in the acute phase of the disease and focuses on the treating early complications of the disease. Long-term health consequences of the infection have not yet been fully identified. A special group of patients with comorbidities, including neoplastic disease for whom the interpretation and management of symptoms is a major challenge.

CASE PRESENTATION

In this case report, we present a 73-year-old woman with recently diagnosed gastric adenocarcinoma in whom we diagnosed orthostatic hypotonia in the aftermath of SARS-CoV-2 infection. We administered thiethylperazine maleate 6.5 mg daily. Additionally, we advised the patient to slowly lift from the recumbent position, raise the headboard, take meals in small portions, and increase fluid intake. These pharmacological and nonpharmacological measures resulted in sustained relief of dizziness and nausea.

CONCLUSIONS

The occurrence of orthostatic hypotonia seems a possible late sequela of SARS-CoV-2 infection, and simple measures appeared sufficient to achieve sustained symptom control.

Topics: Aged; COVID-19; Female; Home Care Services; Humans; Muscle Hypotonia; Pandemics; SARS-CoV-2

PubMed: 35488314
DOI: 10.1186/s40001-022-00685-0

Authors: J M Potter, D B Reid, R J Shaw...

OBJECTIVE

To estimate the prevalence of important side effects in patients with malignant disease who were receiving high doses of morphine as part of their palliative treatment.

DESIGN

Data on patients were collected over 12 months.

SETTING

Two palliative care units in Western Australia.

PATIENTS

19 Patients with malignant disease who were receiving morphine either subcutaneously or orally as the main analgesic. 10 Patients receiving a total daily dose of morphine of at least 500 mg orally or 250 mg parenterally were enrolled in the study. The other 9 patients were enrolled after an important problem thought to be related to the morphine had been identified. All of the patients were taking drugs to supplement the treatment.

INTERVENTIONS

The dose of morphine or route of administration, or both, was changed in three patients.

MAIN OUTCOME MEASURE

Determination of the prevalence of side effects in the patients. Assessment of the relation of any side effects with the supplemental drugs taken by the patients.

MAIN RESULTS

Plasma morphine and electrolyte concentrations were measured and a full history taken for each patient. Thirteen of the 19 patients had an important side effect; 12 of them had myoclonus and one had hyperalgesia of the skin. Plasma morphine concentrations were similar in patients with and without myoclonus, ranging from 158 to 3465 nmol/l and 39 to 2821 nmol/l respectively. Eight of the patients with side effects were taking an antipsychotic drug concurrently compared with none of those without side effects. A greater proportion of patients with side effects were taking the antinauseant drug thiethylperazine (6/13 v 2/6) and at least one non-steroidal anti-inflammatory drug (10/13 v 2/6), whereas a smaller proportion were taking a glucocorticosteroid (3/13 v 4/6). The estimated prevalence of important side effects in the total population of patients receiving palliative treatment in the two units was 2.7-3.6%.

CONCLUSIONS

Myoclonus as a side effect of treatment with morphine is more likely to occur in patients taking antidepressant or antipsychotic drugs as antiemetics or as adjuvant agents or non-steroidal anti-inflammatory drugs for additional analgesia. If a patient develops myoclonus the best approach may be to change the supplemental treatment.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antiemetics; Antipsychotic Agents; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Middle Aged; Morphine; Myoclonus; Neoplasms; Palliative Care

PubMed: 2475196
DOI: 10.1136/bmj.299.6692.150

Authors: Markus Krohn, Cathleen Lange, Jacqueline Hofrichter...

In Alzheimer disease (AD), the intracerebral accumulation of amyloid-β (Aβ) peptides is a critical yet poorly understood process. Aβ clearance via the blood-brain barrier is reduced by approximately 30% in AD patients, but the underlying mechanisms remain elusive. ABC transporters have been implicated in the regulation of Aβ levels in the brain. Using a mouse model of AD in which the animals were further genetically modified to lack specific ABC transporters, here we have shown that the transporter ABCC1 has an important role in cerebral Aβ clearance and accumulation. Deficiency of ABCC1 substantially increased cerebral Aβ levels without altering the expression of most enzymes that would favor the production of Aβ from the Aβ precursor protein. In contrast, activation of ABCC1 using thiethylperazine (a drug approved by the FDA to relieve nausea and vomiting) markedly reduced Aβ load in a mouse model of AD expressing ABCC1 but not in such mice lacking ABCC1. Thus, by altering the temporal aggregation profile of Aβ, pharmacological activation of ABC transporters could impede the neurodegenerative cascade that culminates in the dementia of AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Brain; Disease Models, Animal; Humans; Mice; Mice, Knockout; Mice, Transgenic; Microvessels; Multidrug Resistance-Associated Proteins; Protein Multimerization

PubMed: 21881209
DOI: 10.1172/JCI57867