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At least 19 recordsLinked to original sources

PubMedDate not supplied

Parametric evaluation of methotrimeprazine-midazolam-ketamine and methotrimeprazine-midazolam-ketamine-xylazine combination in dogs.

PURPOSE: To evaluate the parameters of dogs anesthetized by different dissociative drugs protocols through continuous intravenous infusion. METHODS: Thirty healthy dogs of both sexes were assigned randomly to three groups (G1, G2, and G3). G1 was administered with methotrimeprazine as a pre-anesthetic medication, intravenously midazolam-ketamine as bolus for induction and midazolam-ketamine by continuous intravenous infusion for a 60 minute-period of maintenance. G2: the same as for G1. plus an increase in the midazolam dose during maintenance. G3: the same treatment as for G2, plus the addition of xylazine during maintenance. Immediately after induction the anesthetic maintenance started, and measures were taken 15 minutes after pre-medication, at 10 minutes intervals, during maintenance (M0 to M7). RESULTS: Bradycardia, atrioventricular blockage, bradypnea and hypoxemia were shown in G3. G1 and G2 showed a slight hypotension only. CONCLUSION: There were some advantages by using the continuous intravenous via: no parameters oscillation and reduction in the anesthetic recovery period. The increase in midazolam dose brought about little parametric variations which were greater when xylazine was used, with a consequent hypoxemia, bradyarrhytmia, and decrease in respiratory frequency and minute volume.

Anesthesia Recovery Period↗

PubMed1982

Plasma and erythrocyte levels of methotrimeprazine and two of its nonpolar metabolites in psychiatric patients.

Methotrimeprazine (levomepromazine) has two major metabolites in man: N-monodesmethyl methotrimeprazine, which is pharmacologically active and almost as potent as the parent drug; and methotrimeprazine sulfoxide, which is much less active. Blood levels and the distribution between plasma and erythrocytes of methotrimeprazine and the two metabolites were studied in five psychiatric patients on oral methotrimeprazine and after incubation of the compounds in blood from healthy volunteers. The concentrations were measured separately in plasma and erythrocytes by gas chromatography with a nitrogen detector, and the concentrations in whole blood were calculated from the plasma and erythrocyte concentrations. In four of the five patients the blood levels of both metabolites were similar to or higher than the levels of the parent drug. A large interindividual variation was observed in the plasma-erythrocyte concentration ratios. The mean ratios in all individuals were 1.76, 0.57, and 3.02 for methotrimeprazine, N-monodesmethyl methotrimeprazine, and methotrimeprazine sulfoxide, respectively. The relatively high blood concentrations of N-monodesmethyl methotrimeprazine suggest that this metabolite may contribute significantly to the therapeutic action and side effects of oral treatment with methotrimeprazine.

Adult↗

PubMed1996

A fatal case of methotrimeprazine overdose.

Fatal ingestion of methotrimeprazine is unusual, and while therapeutic drug levels are established as concentrations between 0.02 to 0.14 mg/L, fatal levels are not. The following describes a case of fatal suicidal ingestion of methotrimeprazine in which the measured concentration of methotrimeprazine in the blood was 4.1 mg/L. In addition, the major metabolites of methotrimeprazine, desmethylmethotrimeprazine, and methotrimeprazine sulfoxide were also measured at 2.0 and 1.8 mg/L, respectively. Methotrimeprazine and its metabolites were also measured in urine, bile, and vitreous humor. These results are compared with other case reports of methotrimeprazine fatalities reported in the literature.

Adult↗

PubMed1976

Pharmacokinetics of methotrimeprazine after single and multiple doses.

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.

Administration, Oral↗

PubMed1988

The effect of methotrimeprazine on arterial blood gases in human volunteers.

Since methotrimeprazine proved to be both an effective tranquilizer and analgesic, its effect in a tranquilizing dose of 0.15 mg/kg on the arterial blood gases was determined in human volunteers. Because of the known potentiating effect of some phenothiazines on the narcotic-analgesic induced respiratory depression and analgesia, the effect of methotrimeprazine on the meperidine-induced respiratory depression was also studied. Before, and at five minute intervals after the administration of the test drugs, PaO2, PaCO2 and pH were determined by a Radiometer Copenhagen Blood Gas Analyzer (Radiometer Copenhagen, 72 Endruvej, Denmark) through a Riley-needle. Continuous ECG lead II tracings were taken during the experiment. No significant decrease in PaO2 or increase in PaCO2 (P less than 0.01) was observed in 6 healthy volunteers (mean age = 25 yrs) after 0.15 mg/kg i.v. methotrimeprazine. In 19 volunteers (mean age = 32 yrs), the intravenous infusion of 1.5 mg/kg meperidine caused significant decrease in PaO2 and increase in PaCO2 five minutes after its administration. The combined administration of both drugs to 6 volunteers (mean age = 23 yr) caused initially the same decrease in PaO2 as after meperidine alone with subsequent increase in PaO2 over normal levels, however, the PaCO2 significantly increased both as compared to baseline values and as compared with meperidine alone. The pH reductions after the combination of both drugs were greater than after meperidine alone, which in combination with the PaCO2 values confirms the potentiation of meperidine-induced respiratory depression by methotrimeprazine. The results indicate the methotrimeprazine alone causes no significant respiratory depression, but it potentiates the respiratory depression caused by meperidine.

Adult↗

PubMed1996

Antipsychotic and anxiolytic properties of risperidone, haloperidol, and methotrimeprazine in schizophrenic patients.

The subjects were 62 patients hospitalized for acute exacerbations of schizophrenia and were randomly assigned to receive risperidone (mean dose, 7.4 mg/day), haloperidol (7.6 mg/day), or methotrimeprazine (100 mg/day) for 4 weeks. Clinical improvement, defined a priori as a 20% reduction in total Positive and Negative Syndrome Scale (PANSS) scores at end point, was attained by 81% of the risperidone patients, 60% of the haloperidol patients, and 52% of the methotrimeprazine patients (p < 0.05). The reductions in total PANSS and Clinical Global Impression Scale severity scores from baseline to end point were significantly greater in the risperidone patients than in the other two groups. Reductions in scores on the Psychotic Anxiety Scale were significantly greater in the risperidone patients than the methotrimeprazine patients; the difference between haloperidol and methotrimeprazine was not significant. Extrapyramidal symptoms (scores on the Extrapyramidal Symptom Rating Scale) were more severe in the haloperidol patients than in the other two groups, but few differences were apparent between risperidone and methotrimeprazine patients. It is concluded that risperidone is an effective antipsychotic and anxiolytic agent in schizophrenic patients.

Adolescent↗

PubMed2001

The effects of atropine and methotrimeprazine on the epinephrine-induced arrhythmias in halothane-anesthetized dogs.

The effects of atropine and methotrimeprazine on epinephrine-induced ventricular arrhythmias were evaluated in halothane-anesthetized dogs. Ten mixed-breed dogs were assigned to 3 treatments (saline, atropine, and methotrimeprazine) in a randomized complete block design. Anesthesia was induced and maintained with halothane (1.5 minimum alveolar concentration) in oxygen. Controlled ventilation was used throughout to maintain eucapnia. Saline, atropine (0.05 mg/kg, i.v.) or methotrimeprazine (0.5 mg/kg, i.v.) were administered and, 5 minutes later the arrhythmogenic dose of epinephrine (ADE) was measured by i.v. infusion of progressively increasing infusion rates of epinephrine, until the ventricular arrhythmia criterion was met (at least 4 ectopic ventricular contractions (EVCs) during a 15-second period). Data were analyzed using a student's t-test for ADE values and multivariate profile analysis for heart rate (HR), arterial blood pressure (ABP), and rate pressure product (RPP). The ADE increased in atropine- and methotrimeprazine-treated groups, whereas 1 and 4 animals from these groups did not develop any ventricular arrhythmia, respectively. Epinephrine induced multiform premature ventricular contractions (PVCs) in the atropine group, whereas ventricular escape beats were observed in the control and methotrimeprazine groups. Heart rate and RPP decreased, and ABP increased at the time of ADE observation in the control group. Epinephrine infusion in the atropine group caused marked increases in HR, ABP, and RPP, which were associated with pulsus alternans in 2 animals. It was concluded that 1) the presence of cholinergic blockade influences the type of ventricular arrhythmia induced by epinephrine; 2) increased ADE values recorded following atropine administration must be cautiously interpreted, since in this situation the PVCs were associated with signs of increased myocardial work and ventricular failure; and 3) the use of a broader arrhythmia criterion (EVCs instead of PVCs) may not allow a direct comparison between ADE values, since it includes ventricular arrhythmias mediated by different mechanisms.

Analgesics, Non-Narcotic↗

PubMed1991

Methotrimeprazine versus meperidine and dimenhydrinate in the treatment of severe migraine: a randomized, controlled trial.

STUDY OBJECTIVE: To compare the effectiveness of IM administration of methotrimeprazine, a non-narcotic, nonaddicting phenothiazine derivative, with that of a combination of meperidine and dimenhydrinate in the treatment of severe migraine. DESIGN: Double-blind, randomized, controlled trial. SETTING: University hospital emergency department. PARTICIPANTS: Consecutive adult patients with migraine who met eligibility criteria. INTERVENTIONS: Random allocation to receive IM injections of either 37.5 mg methotrimeprazine (Levoprome, Nozinan) or 75 mg meperidine (Demerol) combined with 50 mg dimenhydrinate (Dramamine, Gravol). MEASUREMENTS AND MAIN RESULTS: The 37 patients in each group who completed the study were similar in all demographic and clinical characteristics. There were no statistical differences in pain intensity one hour after treatment, change in pain intensity, or pain relief as measured on a visual-analog scale; need for additional analgesia; persistence of nausea or vomiting; adverse effects; or follow-up status, except for prolonged drowsiness, in the group receiving methotrimeprazine. CONCLUSION: Methotrimeprazine is comparable to meperidine with dimenhydrinate for treating severe migraine and may be considered an effective, nonaddicting, IM alternative to narcotics for the management of this problem.

Adolescent↗

PubMed1983

Interactions of morphine and methotrimeprazine in mouse and man with respect to analgesia, respiration and sedation.

Interactions between morphine and methotrimeprazine have been studied in mice and man with respect to analgesia or antinociceptive activity, respiratory effects and sedation. The volunteer study was a double-blind cross-over trial with 10 volunteers. In mice, methotrimeprazine only possessed antinociceptive activity in doses which caused marked sedation. However, small non-sedative doses of methotrimeprazine potentiated the analgesic action of morphine. The volunteer study did not confirm this finding in man. Methotrimeprazine 7.5 mg i.m. caused significant sedation, but did not alter the effects of morphine 5 mg on pain threshold or ventilatory response to carbon dioxide.

Adult↗

PubMed1982

Chlorpromazine, methotrimeprazine, and metabolites. Structural changes accompanying the loss of neuroleptic potency by ring sulfoxidation.

The 3-dimensional molecular structures of methotrimeprazine, methotrimeprazine sulfoxide, and chlorpromazine sulfoxide were examined by X-ray crystallography. Previous studies of their dopamine receptor binding affinities have indicated that both chlorpromazine sulfoxide and methotrimeprazine sulfoxide lack neuroleptic potency. The crystal structures of methotrimeprazine and its sulfoxide were similar to the previously published structure of chlorpromazine. The sulfoxide metabolite of chlorpromazine, on the other hand, had a different conformation of the side chain. A boat axial conformation of the sulfoxy group was found for both metabolites. The crystal structures suggest that the apparent loss of neuroleptic potency by biotransformation of the phenothiazine drugs to their ring sulfoxides is caused by the introduction of the sulfoxide group itself, and not by concurrent conformational changes in the rest of the molecule.

Animals↗

PubMed2005

An open study of methotrimeprazine in the management of nausea and vomiting in patients with advanced cancer.

INTRODUCTION: Nausea and vomiting are distressing symptoms affecting between 20% and 70% of patients with advanced cancer. Methotrimeprazine is a phenothiazine antipsychotic used in palliative care for the management of terminal agitation and nausea/vomiting but there is only anecdotal evidence to support its use in palliative care. AIM: To establish whether nausea/vomiting in palliative care patients is improved by the administration of low-dose methotrimeprazine. METHODS: Patients with advanced malignancy were entered at different treatment levels according to symptom severity. The dose was altered according to response (minimum dose 6.25 mg daily po, maximum 25 mg by 24-h subcutaneous infusion). Symptoms and side effects were recorded daily from 0 (baseline) to day 5 using a four-point scale. Any improvement in nausea/vomiting score was taken as a response. RESULTS: Sixty-five patients were entered. The cause of nausea and vomiting was multifactorial in the majority of patients, 35/65 (54%). As expected in a study of patients with poor performance status, the attrition rate was high. Of 53 patients evaluable for response at day 2, 33 (62%) showed some improvement in nausea or vomiting. At day 5, improvement was seen in 20/34 (58%). There was no significant change in "side effects" from baseline with time. CONCLUSION: These results suggest that methotrimeprazine has antiemetic activity.

Adult↗

PubMed1995

Ulcerative skin reaction from subcutaneous infusion of isotonic methotrimeprazine and diamorphine.

We report an ulcerative skin reaction resulting from a subcutaneous infusion of isotonic methotrimeprazine and diamorphine. Skin reactions are a recognized side effect of this treatment, although they are reduced by the use of the isotonic formulation of methotrimeprazine. Frank ulceration has not been previously reported. It occurred in our patient despite low doses of diamorphine and methotrimeprazine, an isotonic formulation, and a short infusion time.

Adult↗

PubMed2000

Determination of methotrimeprazine in pharmaceutical preparations by visible spectrophotometry.

A spectrophotometric method is described for determination of methotrimeprazine (levomepromazine). The aim of this work was to develop a simple, rapid, precise, and accurate visible spectrophotometric method for determination of methotrimeprazine in tablet, oral solution, and injection. The method is based on methotrimeprazine reaction with bromophenol blue, resulting in a stable, light yellow-green ion-pair complex that, after extraction with chloroform, presented maximum absorption at 409 nm. Beer's law was obeyed in the concentration range from 5.0 to 25.0 micrograms/ml. The proposed standardized method was applied to commercially available and simulated samples. The accuracy of the method was confirmed by recovery tests.

Antipsychotic Agents↗

PubMed1992

A combination of methotrimeprazine, midazolam and guaiphenesin, with and without ketamine, in an anaesthetic procedure for horses.

A combination of 0.5 mg/kg of methotrimeprazine, 0.1 mg/kg of midazolam and 100 mg/kg of a 10 per cent guaiphenesin solution was investigated for the induction of recumbency in 15 horses; the addition of 1.6 mg/kg of ketamine was also evaluated in 15 horses and anaesthesia was maintained with halothane in oxygen. The horses became recumbent quickly and smoothly and they recovered quietly, with little ataxia. Tachycardia occurred after induction, but no other changes from pre-operative values were observed until halothane in oxygen had been given, when hypothermia, hypotension, bradypnoea, hyperoxaemia, respiratory acidosis and decreased respiratory minute volume developed. Horses given ketamine in addition to methotrimeprazine, midazolam and guaiphenesin were easier to intubate and recovered more quickly than horses receiving only methotrimeprazine, midazolam and guaiphenesin.

Anesthesia↗

PubMed1996

Acute dystonic reaction to methotrimeprazine in hypoparathyroidism.

OBJECTIVE: To report a case of acute dystonic reaction to methotrimeprazine in a patient with untreated hypoparathyroidism, emphasizing the potential increased sensitivity of hypocalcemic patients to the extrapyramidal adverse effects of antipsychotic drugs. CASE SUMMARY: An 80-year-old man who had untreated hypoparathyroidism and chronic hypocalcemia developed an acute dystonic reaction 20 minutes after ingestion of methotrimeprazine 25 mg. His medical history included an ill-defined psychiatric disorder for which he had been treated with methotrimeprazine several years earlier. The patient denied having any other diseases or taking any other medications. After 4 days, the disorientation, psychomotor restlessness, dystonic grimacing, protrusion of the tongue, and speech difficulties disappeared, despite a remaining low serum calcium concentration. DISCUSSION: A possible mechanism, by which striatal calmodulin-mediated adenylate cyclase activation is inhibited by the combined effects of phenothiazines and hypocalcemia, is discussed. CONCLUSIONS: In this patient, it is not possible to ascertain whether the dystonic reaction was due to hypocalcemia, phenothiazine administration, or both. However, it is suggested that patients with hypocalcemia may be sensitive to the extrapyramidal adverse effects of antipsychotics. In addition, acute unexpected dystonic reactions to a small dose of antipsychotics warrants measurement of the patient's serum calcium concentration.

Aged↗

PubMed1976

Inhibition of thalamic and hypothalamic somatosensory evoked potentials by stimulation of substantia nigra and its modification by morphine and methotrimeprazine (levomepromazine).

A brief electrical stimulation of the substantia nigra induced a marked and long lasting inhibition of the somatosensory evoked potentials recorded from the centrum medianum of the thalamus (CM) and posterior hypothalamic area (PHA) following sciatic stimulation in unanesthetized rabbits. The nigral inhibitory effect on CM was prolonged by the administration of morphine (4 mg/kg i.v.) but not influenced by that of methotrimeprazine (2-4 mg/kg i.v.). In contrast, the nigral inhibitory effect on PHA was enhanced by the injection of methotrimeprazine (2 mg/kg i.v.), but not changed by that of morphine (4 mg/kg i.v.). These results indicate that the inhibitory system originating from the substantia nigra operates on the somatosensory transmissions from the peripheral nerve to the thalamus and hypothalamus, and that morphine or methotrimeprazine in small doses induced a selective potentiation of the nigral inhibitory influence on the thalamus or hypothalamus, respectively.

Animals↗

PubMed1982

Differential stereoselectivity of methotrimeprazine enantiomers for selected central nervous system receptor types.

Optical isomers of methotrimeprazine, an analgesic/neuroleptic, were investigated with respect to their ability to interact with six receptor types or subtypes. Bovine caudate nucleus tissue homogenates provided the dopamine, opiate, and serotonin receptor populations studied in these experiments. The radioligands used in saturation and binding competition experiments were tritiated dopamine, spiperone, dihydromorphine, 5-L-methionine enkephalin, naloxone, and 5-hydroxytryptamine. Saturation experiments verified acceptable performance of these in vitro receptor assay systems and indicated that a one-site binding model was adequate for each of these ligands under the experimental conditions employed. The competition experiments exhibited statistically significant (p less than 0.05) differences in isomeric effects only for dopamine and 5-hydroxytryptamine receptors. The more active isomer, levorotatory methotrimeprazine, was shown to be pharmacodynamically equivalent to chlorpromazine at these receptor types. When the magnitude of receptor stereoselectivity is plotted against an estimate of the more active isomer's affinity for that particular receptor, an excellent correlation is observed. This suggests that a high degree of stereoselectivity characterizes a highly specific drug/receptor interaction. These findings are compatible with the conclusion that methotrimeprazine does not produce analgesia via a direct action upon opiate receptors.

Animals↗

PubMed1976

GLC determination of methotrimeprazine and its sulfoxide in plasma.

A GLC method, based on flame-ionization detection, was developed for the assay of methotrimeprazine and its sulfoxide in plasma. For a 6-ml aliquot, the sensitivity was 2-3 ng/ml for the unchanged drug and 4-5 ng/ml for the sulfoxide. The coefficient of variation, calculated from duplicate analyses of plasma samples, was 8-15% for concentrations between 10 and 100 ng/ml. Patients treated with orally administered methotrimeprazine had higher plasma levels of the sulfoxide than of unmetabolized drug. The method also was applied to the analysis of promazine and chlorpromazine in patient plasma.

Chromatography, Gas↗