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Hospital Medicine (London, England :... Aug 1999Levomepromazine (previously known as methotrimeprazine) has a broad range of beneficial effects in the terminal phase of many illnesses, resulting from its combined... (Review)
Review
Levomepromazine (previously known as methotrimeprazine) has a broad range of beneficial effects in the terminal phase of many illnesses, resulting from its combined antipsychotic, anxiolytic and sedative actions. Levomepromazine can safely be administered in a continuous subcutaneous infusion with most other commonly used drugs in palliative care.
Topics: Antipsychotic Agents; Humans; Methotrimeprazine; Psychomotor Agitation; Psychotic Disorders; Terminal Care; Terminally Ill
PubMed: 10621810
DOI: 10.12968/hosp.1999.60.8.1175 -
EMBO Molecular Medicine Jan 2024Japanese encephalitis virus (JEV) pathogenesis is driven by a combination of neuronal death and neuroinflammation. We tested 42 FDA-approved drugs that were shown to...
Japanese encephalitis virus (JEV) pathogenesis is driven by a combination of neuronal death and neuroinflammation. We tested 42 FDA-approved drugs that were shown to induce autophagy for antiviral effects. Four drugs were tested in the JE mouse model based on in vitro protective effects on neuronal cell death, inhibition of viral replication, and anti-inflammatory effects. The antipsychotic phenothiazines Methotrimeprazine (MTP) & Trifluoperazine showed a significant survival benefit with reduced virus titers in the brain, prevention of BBB breach, and inhibition of neuroinflammation. Both drugs were potent mTOR-independent autophagy flux inducers. MTP inhibited SERCA channel functioning, and induced an adaptive ER stress response in diverse cell types. Pharmacological rescue of ER stress blocked autophagy and antiviral effect. MTP did not alter translation of viral RNA, but exerted autophagy-dependent antiviral effect by inhibiting JEV replication complexes. Drug-induced autophagy resulted in reduced NLRP3 protein levels, and attenuation of inflammatory cytokine/chemokine release from infected microglial cells. Our study suggests that MTP exerts a combined antiviral and anti-inflammatory effect in JEV infection, and has therapeutic potential for JE treatment.
Topics: Animals; Mice; Encephalitis Virus, Japanese; Methotrimeprazine; Neuroinflammatory Diseases; Encephalitis, Japanese; Antiviral Agents; Autophagy; Anti-Inflammatory Agents
PubMed: 38177535
DOI: 10.1038/s44321-023-00014-w -
BMJ Open Sep 2019Methotrimeprazine is commonly used for the management of nausea but never tested formally against other drugs used in this setting. The aim was to demonstrate superior... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Methotrimeprazine is commonly used for the management of nausea but never tested formally against other drugs used in this setting. The aim was to demonstrate superior antiemetic efficacy.
DESIGN
Double-blind, randomised, controlled trial of methotrimeprazine versus haloperidol.
SETTING
11 palliative care sites in Australia.
PARTICIPANTS
Participants were >18 years, had cancer, an average nausea score of ≥3/10 and able to tolerate oral medications. Ineligible patients had acute nausea related to treatment, nausea for which a specific antiemetic was indicated, were about to undergo a procedure or had received either of the study drugs or a change in glucocorticoid dose within the previous 48 hours.
INTERVENTIONS
Based on previous studies, haloperidol was used as the control. Participants were randomised to encapsulated methotrimeprazine 6·25 mg or haloperidol 1·5 mg one time or two times per day and assessed every 24 hours for 72 hours.
MAIN OUTCOME MEASURES
A ≥two-point reduction in nausea score at 72 hours from baseline. Secondary outcome measures were as follows: complete response at 72 hours (end nausea score less than 3), response at 24 and 48 hours, vomiting episodes, use of rescue antiemetics, harms and global impression of change.
RESULTS
Response to treatment at 72 hours was 75% (44/59) in the haloperidol (H) arm and 63% (36/57) in the methotrimeprazine (M) arm with no difference between groups (intention-to-treat analysis). Complete response rates were 56% (H) and 51% (M). In the analysis, there was no difference in response rates: (85% (44/52) (H) and 74% (36/49) (M). Complete response rates were 64% (H) and 59% (M). Toxicity worse than baseline was minimal with a trend towards greater sedation in the methotrimeprazine arm.
CONCLUSION
This study did not demonstrate any difference in response rate between methotrimeprazine and haloperidol in the control of nausea.
TRIAL REGISTRATION NUMBER
ACTRN 12615000177550.
Topics: Antiemetics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Female; Glucocorticoids; Haloperidol; Humans; Male; Methotrimeprazine; Middle Aged; Nausea; Neoplasms; Palliative Care; Treatment Outcome
PubMed: 31515428
DOI: 10.1136/bmjopen-2019-029942 -
American Journal of Obstetrics and... Jul 1966
Comparative Study
Topics: Anesthesia, Obstetrical; Female; Humans; Meperidine; Methotrimeprazine; Pregnancy; Scopolamine; Tranquilizing Agents
PubMed: 5940065
DOI: 10.1016/s0002-9378(16)34738-x -
Canadian Medical Association Journal Apr 1983
Topics: Anxiety; Burns; Humans; Methotrimeprazine; Pain
PubMed: 6831331
DOI: No ID Found -
Journal of Palliative Care 2013This retrospective chart review assessed the efficacy, dose, and safety of methotrimeprazine in palliating end-of-life symptoms in children and infants.
OBJECTIVE
This retrospective chart review assessed the efficacy, dose, and safety of methotrimeprazine in palliating end-of-life symptoms in children and infants.
METHODS
A retrospective chart review was conducted of 18 hospitalized pediatric patients who were treated with methotrimeprazine in their last two weeks of life. Data collected included age, diagnosis, symptoms, methotrimeprazine dose, route, efficacy, and any documented adverse effects.
RESULTS
Patients' ages ranged from 16 days to 17 years. Underlying conditions included malignancies, trauma, and various neurodegenerative and congenital diseases. All patients (n = 18) were treated for symptoms of agitation, delirium, or restlessness. Most patients also experienced respiratory secretions/congestion (n = 15), pain (n = 13), and/ or dyspnea (n = 9). Less common symptoms included nausea/emesis (n = 5) and spasticity (n = 1). Methotrimeprazine dosages ranged from 0.02 mg/kg/dose to 0.5 mg/kg/dose. Routes of administration included intravenous (n = 13), oral/gastrostomy tube (n = 6), or subcutaneous (n = 4). Sedation (n = 6) was the only documented adverse effect, although when agitation was present, this was potentially an intended and perceived-to-be-beneficial effect.
CONCLUSION
Methotrimeprazine, an old drug with diverse receptor activity and multiple routes of administration, appears to be an effective tool in treating complicated end-of-life symptoms in children and infants. This study provides a foundation for analysis with prospective and comparative trials, which may further quantify its benefit.
Topics: Adolescent; Antipsychotic Agents; Child; Child, Preschool; Delirium; Dyspnea; Humans; Infant; Infant, Newborn; Methotrimeprazine; Nausea; Pain Management; Palliative Care; Psychomotor Agitation; Retrospective Studies; Safety
PubMed: 24380217
DOI: No ID Found -
Journal of Clinical Psychopharmacology Feb 2017
Topics: Adult; Dopamine Antagonists; Female; Humans; Jews; Methotrimeprazine; Sleep Initiation and Maintenance Disorders; Stevens-Johnson Syndrome
PubMed: 28027113
DOI: 10.1097/JCP.0000000000000641 -
Clinical Pharmacology and Therapeutics Apr 1976Concentrations of methotrimeprazine and a metabolite, methotrimeprazine sulfoxide, were measured in plasma after a single intramuscular dose and after single and...
Concentrations of methotrimeprazine and a metabolite, methotrimeprazine sulfoxide, were measured in plasma after a single intramuscular dose and after single and multiple oral doses of methotrimeprazine. The highest plasma concentrations of methotrimeprazine were found 30 to 90 min after intramuscular injection, and 1 to 3 hr after oral administration. On average 50% of orally administered drug reached the general circulation as unchanged methotrimeprazine. The apparent volume of distribution (Vbeta) was 23 to 42 L/kg body weight, and the biologic half-life, 15 to 30 hr. The sulfoxide could not be traced in plasma after a 25-mg intramuscular dose, but was found in higher plasma concentrations than the unmetabolized drug after single and multiple oral doses. This could be due to oxidation of the drug either in the gastrointestinal lumen or in the intestinal wall, or during its first passage through the liver. The apparent half-life of the sulfoxide was on average 30% shorter than the half-life of methotrimeprazine.
Topics: Administration, Oral; Half-Life; Humans; Injections, Intramuscular; Kinetics; Male; Methotrimeprazine; Middle Aged; Sulfoxides
PubMed: 1269194
DOI: 10.1002/cpt1976194435 -
The Medical Letter on Drugs and... Jun 1967
Comparative Study
Topics: Humans; Meperidine; Methotrimeprazine; Morphine; Pain; Preanesthetic Medication
PubMed: 6035364
DOI: No ID Found -
The American Journal of Psychiatry Mar 1964
Topics: Bipolar Disorder; Dementia; Geriatrics; Mental Disorders; Methotrimeprazine; Psychoses, Alcoholic; Psychotic Disorders; Schizophrenia; Toxicology; Trimeprazine
PubMed: 14129294
DOI: 10.1176/ajp.120.9.905