Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LEVOMEPROMAZINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources

A kinetic study on the phenothiazine dependent oxidation of NADH by bovine ceruloplasmin.

Tranquillizing drugs of the phenothiazine class form charge-transfer complexes with a ceruloplasmin-Cu(II) ion [De Mol NJ. 1985 Biochim Pharmacol 34, 2605-2609], the interaction resulting in a stimulatory effect on the ceruloplasmin catalyzed oxidation of catecholamines and NADH; the latter used as substrate in the present study. A good correlation between stability of the enzyme-drug complex and electron donor ability of the phenothiazine molecule was obtained for drugs with an aliphatic propyl side chain in 10-position (promazine > chlorpromazine > triflupromazine). The hydrofobic methyl group in the side chain of levomepromazine appeared to reduce the stability. A simple correlation between specific efficiency of the enzyme-drug complex and electron donor ability was not obtained (chlorpromazine > promazine = levomepromazine > triflupromazine). The Km-values, characterizing the reaction between NADH and the different enzyme-drug complexes, were estimated. The data suggest that the enzyme-chlorpromazine complex has the best affinity for NADH. The stimulatory effect of levomepromazine closely followed that of promazine.

Animals↗

Phenothiazine drug metabolites: dopamine D2 receptor, alpha 1- and alpha 2-adrenoceptor binding.

The in vitro binding affinities of levomepromazine, chlorpromazine, fluphenazine, perphenazine and methoxypromazine and their main metabolites to dopamine D2 receptors, alpha 1- and alpha 2-adrenoceptors in rat brain, were examined using [3H]spiperone, [3H]WB 4101 and [3H]yohimbine binding. All compounds had 10-500 times lower affinities to alpha 2-adrenoceptors than to dopamine D2 receptors and alpha 1-adrenoceptors. Ring-hydroxylated and N-demethylated metabolites had relative potencies for dopamine D2 receptor and alpha 1-adrenoceptor binding ranging from 20 to 70%, compared to that of the parent drugs. The ring sulphoxides of levomepromazine, chlorpromazine and perphenazine, except dextro levomepromazine sulphoxide, were virtually inactive in all binding systems. The results indicate that the metabolites having the highest binding affinities for dopamine D2 receptor and alpha 1-adrenoceptor binding may contribute significantly to the therapeutic effect and side-effects of the drugs, and should be measured together with the parent drugs in blood level-effect studies.

Animals↗

Effects of neuroleptics displaying antidepressant activity on behavior of rats in the forced swimming test.

Levomepromazine, thioridazine and cis-chlorprothixene, neuroleptics with antidepressant activity, trans-chlorprothixene, the therapeutically inactive isomer of chlorprothixene, clozapine, an atypical neuroleptic, and imipramine, a classical antidepressant, were studied in the forced swimming test in rats after single or chronic administration. Levomepromazine (1.5 mg/kg), clozapine (2.5 and 5.0 mg/kg) and imipramine (10 mg/kg) after single administration, 1 hr before the test, shortened the period of the immobility. After chronic administration only imipramine (10 mg/kg orally, twice daily, for 10 days) diminished the immobility. Levomepromazine, thioridazine, cis-chlorprothixene and trans-chlorprothixene (1.5 mg, orally, twice daily, for 10 days), 15-18 hr after the last dose did not influence the immobility, although the behavioral parameters in the open field test were not depressed. It is concluded that the forced swimming test is not a suitable pharmacological model for revealing antidepressant activities of certain neuroleptics that are useful in treating certain forms of human depression.

Animals↗

[Comparative study of the effect of some psychotropic substancces on the activity of brain Na+, K+-ATPase in vitro].

The activity of Na+, K+-ATPase from bovine brain in vitro was studied as affected by some neuroleptics (levomepromazine, chlorpromazine, perphenazine and haloperidol), antidepressants (imipramine and iproniazid) and psychostimulants (amphetamine) as well as by benactyzine and procaine. The degree of the enzyme inhibition by these drugs estimated by means of I 50 and apparent inhibitor constants (Ki) or rate constants (k) was different. Sensitivity of the brain Na+, K+-ATPase to the drugs decreased in the following order: levomepromazine, chlorpromazine, perphenazine, haloperidol, imipramine, iproniazid, benactyzine, procaine and amphetamine. Competition for the enzyme was revealed between sodium and some of the drugs investigated (levomepromazine, chlorpromazine, perphenazine and impramine) as well as between potassium and other drugs (haloperidol, genactyzine and amphetamine). It is suggested that the inhibition of the brain Na+, K+-ATPase by psychotropic drugs may be a part in the biochemical mechanism of their sedative-tranquilizing activity.

Adenosine Triphosphatases↗

[An emergency cesarean section using general anesthesia for a patient with schizophrenia].

A 27 year-old female in 39th week gestation with schizophrenia underwent an emergency Cesarean section using general anesthesia. A diagnosis of schizophrenia was made two years previously, since then oral anti-psychotic drugs such as chlorpromazine had been given to her. In June 1989 she suddenly became excited and generalized muscle rigidity was observed without any triggering episodes. Her excitement was so marked that we had to administer intramuscular levomepromazine 75 mg and diazepam 10 mg to her, but they failed to sedate her adequately. Emergency Cesarean section was scheduled to overcome this situation. Spinal or epidural anesthesia was not indicated because of her vigorous excitement, and anesthesia was induced with thiopental 350 mg and succinylcholine 40 mg. Induction-delivery time was 12 minutes. Pentazocine 30 mg in combination with nitrous oxide was given for the maintenance of anesthesia. Plasma levomepromazine levels were 46.9 ng.ml-1 in the mother and 11.3 ng.ml-1 in the umbilical vein, respectively. The baby's Apgar score was 9 and 1 min and 9 at 5 min after the delivery. The baby developed slight generalized tremor until next day, probably due to effect of levomepromazine given before the Cesarean section. The patient was discharged without any cardiorespiratory trouble and her baby has been doing well so far.

Adult↗

[Inhalation of levopromazine (Nozinan) in the treatment of status asthmaticus].

Levomepromazine reduces histamine-induced bronchial hyperresponsiveness in asthmatics without significant sedation. We present two patients with acute asthma refractory to conventional therapy, who were treated with inhalation of 2.5 mg levomepromazine. Until controlled studies have been done, we suggest that inhalation of levomepromazine be restricted to patients with asthma refractory to conventional therapy.

Administration, Inhalation↗

Effect of single oral doses of various neuroleptic drugs on salivary secretion rate, pH, and buffer capacity in healthy subjects.

The effects of melperone, thioridazine, levomepromazine, and chlorprotixene on salivary secretion rate, pH, and buffer capacity was studied in eight healthy volunteers given single oral doses of placebo or 10, 25, and 50 mg of the drugs in a single-blind crossover design. Both resting and stimulated saliva samples were collected before and every hour for 6h after administration. All drugs reduced secretion rate and lowered pH and buffer capacity, mostly in a dose-dependent manner. The effects of levomepromazine and chlorprotixene were more pronounced than those of melperone and thioridazine.

Adult↗

Antidepressants and endogenous opioid peptide systems.

The influence of antidepressants on the brain and pituitary content of immunoreactive beta-endorphin (ir-beta E) and dynorphin (ir-DYN) was studied in rats. Chronic administration of the first and second generation antidepressants imipramine, citalopram and rolipram, and of the antidepressant neuroleptics levomepromazine and chlorprothixene elevated the level of ir-beta E in the hypothalamus. Imipramine and levomepromazine also increased the level of ir-DYN in this tissue. Imipramine administered chronically potentiated stress-induced as well as morphine analgesia. The results obtained suggest that chronic antidepressants enhance the brain opioid system activity and increase the sensitivity of opiate receptors.

Animals↗

The calcium entry blockers: anti-manic drugs?

The reported property of calcium antagonists as antimanic drugs has been investigated in three models of hyperactivity in mice. The hyperactivity was induced by amphetamine, oxolinic acid or reserpine after inhibition of monoamine oxydase (MAO). Nicardipine (a dihydropyridine derivative) reduces the three hyperactivities, verapamil (a diphenylalkylamine derivative) reduces only oxolinic acid hyperactivity, and diltiazem (a benzothiazepine derivative) was active except in the MAOI-reserpine test. Levomepromazine used as a reference drug reduced the three hyperactivities. The three calcium entry-blockers reduce the different hyperactivities at doses which already decrease motor activity. And so, it seems that their action was not specific. On the contrary, levomepromazine antagonizes MAOI-reserpine induced hypermotility at a dose which is not sedative. These results do not strengthen the property of calcium antagonists as antimanic drugs.

Amphetamines↗

Fluvoxamine and fluoxetine: interaction studies with amitriptyline, clomipramine and neuroleptics in phenotyped patients.

The in vivo pharmacokinetic interaction between two selective serotonin reuptake inhibitors (SSRI) (fluvoxamine, fluoxetine) and tricyclic antidepressants (TCAs) (amitriptyline, clomipramine) or neuroleptics (haloperidol, cyamemazine, levomepromazine, propericiazine) was assessed in 29 in-patients. They were phenotyped twice with dextromethorphan and mephenytoin: first in steady state conditions while under treatment with TCAs or neuroleptics; and also 10 days after an associated treatment with fluvoxamine (150 mg day(-1)) or fluoxetine (20 mg day(-1)). A clear and statistically significant increase in the mean urinary metabolic ratio (MR) of dextromethorphan/dextrorphan and in the mean mephenytoin S/R ratio (S/R) was seen with the fluvoxamine and fluoxetine treatment. The mean MR increased from 0.13 to 0.27 (P<0.01) with fluoxetine and from 0.34 to 0.84 with fluvoxamine (P<0.05). The (dextromethorphan) 'extensive metabolizer' phenotype switched to the 'poor metabolizer' phenotype in six patients by the 10-day fluoxetine treatment, and in two patients by the fluvoxamine treatment. The mean S/R increased from 0.24 to 0.34 (P<0.05) with fluoxetine, and from 0.33 to 0.58 (P<0.002) with fluvoxamine. These results are in agreement with the observed modification of TCA plasma levels after the SSRI association. During fluvoxamine treatment, amitriptyline and clomipramine plasma levels (P<0.06 both) tendentially increased, and those of demethylclomiprarnine decreased (P<0.06). Fluoxetine addition lead to a significant increase (P<0.02) of the desmethylclomipramine plasma levels. Fluvoxamine induced a moderate augmentation of the plasma levels of haloperidol and its reduced metabolite and no change in the plasma levels of cyamemazine and levomepromazine. But patients treated with neuroleptics are to few to draw any firm conclusion. This study suggests, that fluoxetine and fluvoxamine differ in their interaction with the metabolism of some other basic psychotropic drugs, by a mechanism which implies CYP2D6 and CYPmeph and possibly other isoformes of cytochrome P-450. Moreover, the interactions produced varied with the TCA prescribed.

Adult↗

Optimization of the separation of some psychotropic drugs and their respective metabolites by liquid chromatography.

A chemometric procedure is described to optimize the separation of some drugs used in the treatment of psychotic disorders: haloperidol, levomepromazine, risperidone, venlafaxine, carbamazepine and their main metabolites: reduced haloperidol, 9-hydroxy risperidone, desmethyl levomepromazine, desmethyl venlafaxine. The purpose of the procedure is the unambiguous identification and detection in biological fluids. Isocratic reversed-phase liquid chromatography with diode array detection was utilized. An experimental design methodology was carried out in which the experimental response is selectivity. In this way the designs for mixture compounds and for process variables (five variables) was performed which produced 36 experiments to carry out. The desirability function was used to select optimum separation conditions. The procedure provides a chromatogram of well separated solutes.

Acetonitriles↗

A fatal case of amoxapine poisoning under the influence of chronic use of psychotropic drugs.

A 43-year-old woman was found dead in a car in the supine position. She had been suffering from depression for 2 years and hesitation wounds on the left forearm and wrist were observed. On microscopic examination, pulmonary congestion and edema were observed with heart failure cells in many alveoli, thereby suggesting not only acute but also chronic heart failure. Drug screening in the blood by gas chromatography-mass spectrometry (GC-MS) revealed the presence of amoxapine and levomepromazine, and their concentrations in tissues were determined by GC-MS with three-step solvent extraction followed by acetylation. The concentration of amoxapine in the blood and liver was 0.86-1.77 and 18.76microg/ml, respectively; the levels were much higher than the therapeutic level but did not reach the lethal level. The concentrations of levomepromazine in tissues were within the therapeutic level. Based on the pathological and toxicological findings, the cause of death was determined to be amoxapine poisoning on the basis of chronic heart failure due to the chronic use of psychotropic drugs.

Adult↗

A CYP2D6 phenotype-genotype mismatch in Japanese psychiatric patients.

The aim of the present study was to seek a CYP2D6 genotypic-phenotypic discordance possibility in Japanese patients under psychotropic drug treatment where the CYP2D6 status and pharmacodynamic responses differ from those in Caucasian psychiatric patients. Ninety drug-free, healthy volunteers and 14 patients undergoing psychotropic drug treatment were phenotyped for their individual CYP2D6 activity using dextromethorphan as a probe, and then the metabolic ratio (MR) was calculated. For the genotyping, eight mutant alleles of the CYP2D6 genes were identified. Serum concentrations of two frequently co-medicated psychotropic drugs, biperiden and levomepromazine, were determined by GC/MS. Genotyping revealed no poor metabolizers (PMs) enrolled in our study. Healthy volunteers exhibited an identical phenotype-genotype concordance, whereas 7 of the 14 patients had significantly high (p < 0.05) MRs compared with genotype-matched volunteers. Three of the patients who had the extensive metabolizer (EM) genotype had extremely high MRs and were classified as phenotypic PMs. Five patients plus all of the seven high MR patients were treated with levomepromazine and/or biperiden, respectively. Their mean serum steady-state concentrations were 27.4 and 7.6 ng/ml, respectively. A CYP2D6 phenotype-genotype mismatch (phenocopying) can occur in Japanese psychiatric patients receiving clinical doses of some psychotropic drugs where the prevalence of PMs is low and the pharmacodynamic responses to those drugs are enhanced compared to Caucasian patients.

Adult↗

Effectivity of zotepine in refractory psychoses: possible relationship between zotepine and non-dopamine psychosis.

We reported the results of a survey of patients who suffered from schizophrenia with predominate hallucinatory and delusional states, and who had been unresponsive to a variety of antipsychotics like haloperidol but responded more favorably to zotepine. In 10 of the 22 zotepine-responsive patients in this study, there was marked improvement with zotepine. Considering the results from previous drug treatment, the phenothiazines (especially levomepromazine) surpassed the butyrophenones in efficacy, suggesting that zotepine might resemble levomepromazine clinically. After administration of zotepine, cenesthesic hallucination, behavior caused by hallucination, egorrhoe, affective symptoms, and catatonic symptoms were markedly improved. However, insight into disease and negative symptoms were minimally improved after administration of zotepine. Zotepine was effective in the refractory psychoses due to its potent action on the delusional dynamics, in spite of producing little marked improvement in such main symptoms as hallucination and delusion. The authors speculate that zotepine's potent activity at serotonin-1 receptors may lead to a beneficial effect in refractory psychoses, just as in the case of its antimanic effect.

Adolescent↗

The use of therapeutic drug monitoring data to document kinetic drug interactions: an example with amitriptyline and nortriptyline.

Therapeutic drug monitoring data for amitriptyline (AT) and nortriptyline (NT) collected during 10 years (total of 4,278 analyses in 2,937 patients) were evaluated to study how other drugs affect the kinetics at steady state. The distribution of the ratio concentration/daily dose (C/D) in patients treated with the antidepressant only was compared with that in patients on different concomitant drugs. Patients on phenothiazines or dextropropoxyphene had a significantly higher mean C/D of NT than controls, both when AT and when NT had been given. The highest values were seen with levomepromazine and thioridazine. On the contrary, the mean C/D of both AT and NT in patients on carbamazepine was about 50% lower than in those treated with the antidepressant only. Benzodiazepines did not affect the steady-state kinetics of AT or NT. Intraindividual comparisons of the ratio C/D in subjects with analyses performed when off and on concomitant drugs corroborate previous results showing that drugs metabolized by the debrisoquine hydroxylase (CYP2D6) inhibit the metabolism of NT and that carbamazepine induces the metabolism of both AT and NT. Modeling of the dose dependency of the NT interactions with levomepromazine, perphenazine, and thioridazine revealed that the ratio C/D was most affected at low doses of the antidepressant and at high doses of the phenothiazine. The distribution of the doses given was the same in patients on monotherapy as in patients with interacting drugs, which means that many patients treated with phenothiazines had concentrations above the therapeutic range and that most patients treated with carbamazepine had subtherapeutic levels. The present study shows that therapeutic drug monitoring may serve as a valuable tool to discover and quantify drug interactions.

Adolescent↗

Pharmacological approaches other than opioids in chronic non-cancer pain management.

Many pains are controlled by non-addictive procedures ranging from exercise to a variety of analgesic medications. Some pains are controlled by analgesic drugs, but at the cost of intolerable side effects. This is true both for non-steroidal anti-inflammatory drugs and opioids. The worst pains are most often controlled by opioids, but problems of tolerance and addiction limit these successes. This contribution provides a statement on non-addictive, non-opioid drugs which help to control pain. Just as these vary in their success, so they vary also in the strength of the scientific evidence which supports their use. The groups of drugs to be considered can be evaluated in three respects; evidence of analgesic effect in controlled trials; evidence of side-effects compared with control substances and with standard experience; evidence of usefulness in clinical practice. The latter which is the most important for practice often has the least scientific proof. Six main classes of drugs are recognized which provide analgesic effects, other than opioids. 1) Non-steroidal anti-inflammatory drugs are widely accepted as analgesics on the basis of animal studies, numerous controlled investigations and clinical practice. Acetaminophene may not be anti-inflammatory, but is recognized as an effective analgesic which in many other respects resembles the above. 2) Muscle relaxants, e.g. cyclobenzaprine or baclofen have varied actions, but often provide some relief of pain. 3) Antidepressants may be analgesic if they relieve depression which is giving rise to pain. This applies to all anti-depressants. Some antidepressants have been shown to be analgesic in the absence of depression. The best accredited of these is amitriptyline. Antidepressants too have significant side effects. A serotoninergic hypothesis is insufficient to explain the actions of antidepressants in relieving pain in the absence of depression. 4) Phenothiazine neuroleptics (and possibly some others) may be analgesic. Drugs reported to be analgesic include chlorpromazine, fluphenazine, perphenazine, trifluoperazine, methotrimeprazine (levomepromazine) among others. Haloperidol has also been utilized. Well controlled evidence exists with the use of methotrimeprazine (levomepromazine) used as an injection. The analgesic effect of oral neuroleptics is less well established and mostly depends upon clinical observation, withdrawal and re-challenge. 5) Anticonvulsants. 6) Other drugs. Non-steroidal anti-inflammatory drugs and some muscle relaxants, e.g. cyclobenzaprine are best used in the short term. The gastrointestinal side effects of non-steroidal anti-inflammatory drugs have been quite troublesome and over 2% of patients followed over five years are at risk of developing peptic ulceration from such medication. Cyclobenzaprine is best used in short term treatment, but may be used intermittently for chronic pain. Antidepressants, neuroleptics, anticonvulsants and some other drugs can be used long term. Topical analgesic agents may also be used.

Analgesics↗

A study comparing hyoscine hydrobromide and glycopyrrolate in the treatment of death rattle.

This study looked at the efficacy of drug treatment in managing death rattle in a 30-bedded specialist palliative care unit. The study was conducted in two phases. In the first, patients received hyoscine hydrobromide as the antimuscarinic; glycopyrrolate was used in the second phase. The patients in the two phases were well matched for diagnosis, age, sex and duration of death rattle. A noise score scale of 0-3 was used, which was separately validated using a verbal rating scale and noise-meter readings. Noise scores were taken at the start; 30 min after an antimuscarinic drug was administered; an hour after the initial injection if a repeat dose was given at 30 min; and 4-hourly thereafter. Drug charts of all patients with death rattle were analysed to ascertain the amount of each drug given and the cost. The incidence of death rattle was 44% in phase I, and 36% in phase II. The percentage of patients with reduced noise scores 30 min after one injection of hyoscine was significantly greater than after one dose of glycopyrrolate (56% vs 27%, P = 0.002). The need for a second injection after 30 min was less using hyoscine (33% vs 50%, P = 0.03). There was no statistically significant difference in improvement at 1 h, or at the last recorded score before death. A comparison of the cost of drug treatment using hyoscine or glycopyrrolate was made, and the potential reduction in cost per patient in the glycopyrrolate group was largely offset by increased expenditure on other drugs, especially diamorphine, midazolam and levomepromazine. The results of this study suggest that: (1) glycopyrrolate 0.2 mg is less effective at reducing death rattle than hyoscine hydrobromide 0.4 mg when assessed at 30 min, (2) the use of glycopyrrolate may lead to an increased need for other sedative or anti-emetic medication such as diamorphine, midazolam or levomepromazine, and (3) the cost benefit of using glycopyrrolate over hyoscine hydrobromide is a small part of the total drug budget, and may be less than anticipated due to the increased need of these other drugs.

Adult↗

Interaction of alcohol and drugs in fatal poisonings.

In Finnish data from 1995-2000, 1006 fatal poisonings due to alcohol (ethanol), a single drug or both were statistically analysed in retrospect to evaluate the interaction between alcohol and drugs. In 53% of these cases, low concentrations of some common benzodiazepines were present. The median postmortem blood alcohol concentration (BAC) was 3.3 percent per thousand (w/w) in the 615 alcohol poisonings, but significantly lower, ranging from 1.3 to 1.7 percent per thousand, when promazine, doxepin, amitriptyline or propoxyphene were found together with alcohol. When levomepromazine, temazepam or zopiclone were present, the median BAC was also significantly lower, 2.5-2.7 percent per thousand. Citalopram and diltiazem did not exhibit a significant effect. The median BAC was significantly lower in cases with high concentrations than in those with low concentrations of a drug (excluding citalopram), suggesting a positive concentration-effect relationship. Fatal toxicity indices (FTIs) were calculated by relating the number of deaths caused by a drug to the corresponding sales figures. Promazine had an extremely high FTI, followed by levomepromazine, propoxyphene, doxepin and amitriptyline. The other drugs had relatively low FTIs. The results reflect not only the acute toxicity of a given drug-alcohol combination but also the manners of use and abuse of these drugs.

Adult↗