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PubMed1981

[Metabolic interactions of promethazine (author's transl)].

Owing to enzyme induction, the pretreatment of female Wistar rats with promethazine (Prothazin, Atosil) produces a shortening of the hexobarbital sleeping time, a slight increase in the relative liver weight, an increase in the N-demethylation of aminophenazone, the O-demethylation of codeine phosphate, the O-demethylation of p-nitroanisol, the glucuronidation of p-nitrophenol and the NADPH-cytochrome c reductase activity in the 9.000 g supernatant of liver homogenates. Particularly striking are the strong stimulation of the N-demethylation and the also potentiated [in contrast to the findings obtained with dioxopromethazine (Prothanon)] UDP-glucuronyltransferase activity, whereas the cytochrome P-450 concentration shows a slight trend toward increase, but this is not statistically significant. The findings obtained justify the expectation of drug interactions in case of repeated application of promethazine in the framework of a combined therapy.

Animals↗
PubMed1982

Experimental infection with Ancylostoma caninum larvae in mice. VII. Role of promethazine hydrochloride in the rejection of worm burden from the intestine.

Acquired resistance of female swiss albino mice (6 to 8 weeks old) to Ancylostoma caninum infection was demonstrated by the transfer of mesenteric lymph node cells (MLNC) from resistant (sensitised and promethazine treated), sensitised and untreated and non-sensitised and untreated donors to normal recipients of the same isogeneic strain. MLNC from sensitised and promethazine treated donors were more effective in suppressing the rejection mechanism of worm burden in recipients in comparison to the cells obtained from other donor groups; the drug may be exerting an inhibitory action at either the specific lymphoid level (reducing antibodies effect) and at the non-specific amine level.

Ancylostomiasis↗
PubMedDate not supplied

The immunologic response to tobacco antigens in smokers. IV. Effect of heparin, aspirin, promethazine and prednisone.

The effects of heparin, aspirin, promethazine and prednisone on late skin reactions, provoked by tobacco extracts were studied in four groups of 17 patients with coronary artery disease. In all patients, intracutaneous tests were made with four different tobacco preparations, both on the first day of their hospitalisation and after 14 days of therapy. It was found that strongly positive late skin reactions with tobacco extracts were decreased or suppressed in patients taking heparin and in patients taking prednisone, but not in those who were treated with promethazine or with aspirin. This seems to confirm the hypothesis that these reactions are really provoked by a local type III allergy to tobacco antigens.

Adult↗
PubMed1980

[Eeg-effects of promethazine. study on 17 patients (author's transl)].

Changes in EEG and cEEG were studied in two groups of patients premedicated with promethazine in a dosage of 50 mg iv; study group A consisted of patients whose age ranged from 20-50 years and study group B of patients whose age was above 70 years. The observation time was 15 min but in a few patients only it was extended to 60 min. Changes in behaviour were clinically controlled. Blood pressure and pulse-rate measurements were taken at regular intervals. The first taken base line electroencephalogram patterns of the patients in group A were unremarkable. The recordings of the patients in group B showed a high percentage of deviation from normal. The sedative effect of promethazine showed a widespread individual variation as did also the characteristic changes in EEG frequency bands. Psychomotor side-effects were frequently seen. Characteristic changes in EEG were found to be a continuing 20%-50% decline of alpha amplitude mostly combined with an alternation of stability, or a narrowing of the frequency range in the higher beta band. In addition a light increase of delta and theta activity was observed. Blood pressure and pulse-rate showed a light increase.

Adult↗
PubMed1994

Sublethal effects of inorganic mercury on the body growth rate and liver function enzymes of phenobarbitone-pretreated and promethazine-pretreated rabbits.

Hepatotoxic effects of inorganic mercury with and without pretreatment of phenobarbitone and promethazine have been described in experiments on domesticated rabbits. The total body weight and the relative liver weight decreased after mercury treatment under all experimental conditions. After phenobarbitone (PB) treatment, the serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), isocitrate dehydrogenase (ICDH), and lactate dehydrogenase (LDH) activities decreased to 31%, 77%, 20%, and 27%, respectively, whereas the serum alkaline phosphatase (AP) activity increased 54%. After promethazine (PM) treatment, however, the serum GPT activity was inhibited 73%, whereas the serum LDH activity increased 53%. Both hepatic GPT and AP activities decreased after PB (41% and 46%, respectively) and after PM (50% and 52%, respectively) treatments, while the activities of LDH and ICDH increased (after PB: 924% and 108%, respectively; after PM: 147% and 40%, respectively). After mercuric chloride (HgCl2) treatment, the serum GOT, GPT, LDH, and ICDH activities decreased 69%, 83%, 11%, and 48%, respectively. The hepatic GOT, LDH, and AP activities increased 56%, 129%, and 51%, respectively. The administration of HgCl2 in PB-pretreated animals was associated with a decrease in the activities of serum GOT and AP (57% and 69%, respectively), while the ICDH activity increased 27%. The hepatic GOT, GPT, and AP increased 58%, 135%, and 77%, respectively, after mercury treatment, whereas LDH and ICDH were inhibited 78% and 29%.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Oxidoreductases↗
PubMed1993

[Oral premedication with clorazepate dipotassium. Comparison with oral premedication with flunitrazepam and intramuscular premedication with promethazine, pethidine and atropine in adults].

UNLABELLED: The purpose of premedication and the best form have been frequent subjects of controversy among anaesthetists in the past few years. Anxiolysis is now accepted as the main purpose. The preferred route of administration is by mouth. The intention of this study was to examine whether clorazepate dipotassium has the same sedative-hypnotic and anxiolytic effects as i.m. premedication with promethazine, pethidine and atropine. METHODS: A total of 100 patients aged 20-65 years and due to undergo arthroscopy took part in this study. Patients in group I were given 1 mg flunitrazepam p.o. on the evening before the operation and the i.m. premedication described above. The premedication for group II consisted in clorazepate dipotassium, 50 mg on the evening before operation and 25 mg on the morning of the day of the operation. The sedative-hypnotic effects were measured on a four-point scale. The Erlangen anxiety scale (EAS) and a visual analogue scale (VAS) were used to evaluate the anxiolytic effects according to the patient's own and the observer's evaluation of mood. In addition to this, we measured amnesia, heart rate and blood pressure. RESULTS: Clorazepate dipotassium or flunitrazepam p.o. significantly reduces anxiety 1 h after administration as measured by the EAS (P < 0.05) on the evening before the operation. This result was not, however, confirmed by the VAS for self-assessment. Patients who received premedication with clorazepate dipotassium are less anxious on the morning of the operation than patients given flunitrazepam the evening before the operation (P < 0.05); this, however, does not correspond to the VAS results. There were no differences in the other parameters compared. DISCUSSION: Oral premedication with clorazepate dipotassium has the same sedative-hypnotic, anxiolytic and amnestic effects as i.m. premedication with promethazine, pethidine and atropine. The results of this study are better than those obtained by Tolksdorf et al., owing to the higher dosage used in our study (50 mg as against 20 mg). Tolksdorf et al. [21] failed to show any improvement on a placebo. Our results correspond to those of Drautz et al. [2] who used 50 mg of clorazepate dipotassium on the evening before and 25 mg on the morning of the day of the operation.

Administration, Oral↗
PubMed2006

[Differential kinetic spectrophotometric determination of chlorpromazine hydrochloride and promethazine hydrochloride by chemometric method].

Chlorpromazine hydrochloride and promethazine hydrochloride were oxidized fastly resulting in red intermediate product, which was then gradually changed into a colorless product by ammonium cerous sulfate in appropriate acidic medium. The chemometric multivariate calibration methods, such as partial least squares (PLS) and principal components regression (PCR) were applied to the resolution of the kinetic curves to determine these two compounds. The linear ranges are 8.3 - 66.7 mg x L(-1) and 3.3 - 26.7 mg x L(-1) for chlorpromazine and promethazine, respectively. The limits of detections are 2.32 and 0.95 mg x L(-1) for these two compounds, respectively. This method was successfully applied to the analysis of pharmaceutical samples with satisfied results.

English Abstract↗
PubMed1983

Correlations between common tests for assessment of liver damage: indices of the hepatoprotective activity of promethazine in carbon tetrachloride hepatotoxicity.

The effects of promethazine (PM) on different aspects of the hepatotoxic action of CCl4 in the rat were investigated with the objective of finding rapid and reliable indicators of hepatoprotective effects. The study was based on definitive histological assessment of liver damage caused by CCl4 in the presence and absence of PM: PM (78 mumol kg-1, i.p.) protected against CCl4-induced hepatic necrosis 24 h after a low dose of CCl4 (1.3 mmol kg-1) but not against a higher dose (13.0 mmol kg-1). The large increases in plasma activities of GOT, GPT and LDH produced by dosing with CCl4 were partially inhibited by the administration of PM. PM and CCl4 caused a synergistic and long-lasting decrease in body temperature (2-3 degrees C for 8-10 h). Modifying the toxicity with PM, together with a low dose of CCl4, helped to minimize secondary effects of CCl4, to clarify the sequence of toxic events, and to assess the sensitivity of some standard tests of hepatotoxicity. Simultaneous measurement of over 20 commonly used biochemical screening tests in individual animals 3 or 6 h after treatment permitted direct correlation of a wide variety of concentrations, activities and effects. For example, liver CHCl3 concentrations (as a measure of CCl4 metabolism) correlate strongly with increases in diene conjugation of microsomal lipids (as a measure of CCl4-induced lipid peroxidation); malonaldehyde production appears to be less sensitive as a measure of lipid peroxidation in vivo than diene conjugation. The changes induced in each parameter and the correlations between them are discussed with reference to the overall nature of the hepatotoxic reaction and its modification by PM.

Animals↗
PubMed1978

Kinetics and mechanism of oxidation of promazine and promethazine by ferric perchlorate.

The equilibrium constants, kinetics, and mechanism of promazine and promethazine oxidation by ferric perchlorate were investigated at different temperatures and acidities using a stopped-flow spectrophotometric technique. The overall reaction can be represented as follows: (formula: see text) where P+ represents the radical cation corresponding to the phenothiazine derivative. The equilibrium quotients were evaluated at 1.00 M HClO4, 25.0 degrees, and ionic strength 1.0 M. The kinetics of reaction follow the equation: -d[P] divided by dt = k1[Fe3+][P]-k-1[Fe2+][P+] The rate constants k1 and k-1 are independent of acidity and are related to the corresponding equilibrium quotients.

Chemical Phenomena↗
PubMed1982

In vitro adsorption-desorption of fluphenazine dihydrochloride and promethazine hydrochloride by microcrystalline cellulose.

Fluphenazine dihydrochloride and promethazine hydrochloride were adsorbed in vitro from suspensions of the tableting excipient, microcrystalline cellulose. Studies were undertaken to determine how this adsorption phenomenon was affected by the type of phenothiazine derivative, the type of microcrystalline cellulose, and pH and ionic strength adjustment. The smaller the microcrystalline cellulose particle size, the more drug was adsorbed. Changes in the pH, the ionic strength, and the valency of the cation used to adjust the ionic strength all had a major effect on the extent of adsorption. The adsorption process was rapidly and completely reversed in vitro at gastric pH and ionic strength values.

Adsorption↗
PubMed1978

Scanning electron-microscope studies of the endothelium of aortic allografts in the rabbit: effect of azathioprine, prednisolone and promethazine on early cellular invasion.

Aortic allografts in rabbits were observed by scanning electron microscopy 24 hr after transplantation. The extent of the leucocytic invasion could be precisely and reproducibly measured. Azathioprine and prednisolone, whether alone or in combination, given on three occasions--10 hr before, immediately after and again 10 hr after surgery, significantly inhibited the cellular invasion. Promethazine produced a slight, but not statistically significant, effect.

Animals↗
PubMed1996

The role of enteric bacteria in the pathogenesis of fatal cycloheximide intolerance in mice pretreated with dexamethasone, promethazine or nordihydroguaiaretic acid.

As an incidental finding in a separate, ongoing investigation, dexamethasone was shown to sensitise mice fatally to a later challenge with a normally-tolerated dose of cycloheximide. This phenomenon is described here; it is also shown that two unrelated agents, namely promethazine and nordihydroguauaretic acid, duplicated this sensitising effect of the steroid. The three drugs have in common the ability to inhibit powerfully the synthesis of tumour necrosis factor-alpha in response to lipopolysaccharide, and it is suggested that this property is linked to their ability to induce fatal cycloheximide intolerance. Such drug-pretreated mice were protected if given dexamethasone at the time of cycloheximide challenge. An equal degree of protection was conferred on such animals by oral antibiotic treatment known to eliminate the aerobic intestinal flora. This indicated that the three agents induced fatal susceptibility to cycloheximide through the agency of the gut flora. It is proposed that the three drugs act by impairing the hepatic mechanism which normally removes portal vein-borne endogenous lipopolysaccharide, leading to systemic distribution of lipopolysaccharide, which is known from previous work, using a small dose of intraperitoneally injected lipopolysaccharide, to render mice fatally susceptible to a later cycloheximide challenge.

Animals↗
PubMedDate not supplied

Effect of promethazine on the metabolism of chloroquine.

Co-administration of promethazine hydrochloride and chloroquine phosphate resulted in increased blood levels of chloroquine and its metabolites. However, there is no statistical difference between the means obtained for the initial rate of excretion and the total drug excreted within three hours.

Adult↗
PubMed1978

Promethazine hydrochloride: use in patients with Rh isoimmunization.

Twenty-two babies born to 21 mothers were treated prenatally for varying periods of time with promethazine hydrochloride in doses of 150 mg. per day. Seven of the 22 babies required intrauterine transfusions. With the exception of positive clinical impressions in some cases, specific ameliorating effects of the drug in this group could not be demonstrated.

Blood Transfusion, Intrauterine↗
PubMed1982

Fetal heart rate decelerations following the administration of meperidine-promethazine during labor.

A deceleration response lasting up to 7 min was observed in 53 fetuses (out of 1910 studied) following the administration of 75 mg meperidine and 25 mg promethazine intravenously to the mothers during labor. Thirty-six of these fetuses reacted with baseline tachycardia following the deceleration with or without loss of baseline variability. Seven fetuses showed a variable deceleration pattern and six fetuses reacted with a late deceleration pattern following the first deceleration. Two newborns from the group showing a late deceleration pattern were delivered with an apgar score below 7 in 5 min. The probable mechanisms and significance of these changes are discussed.

Anesthesia, Obstetrical↗
PubMedDate not supplied

Induction of avidin in the chick oviduct by tissue damage. Effect of promethazine chloride, CaCl2 and hydrocortisone on local induction.

The local effect of the mechanical induction of avidin by ligature was studied in diethylstilbestrol-primed chicks. The highest induction of avidin was always found in the immediate vicinity of the silk ligature of the oviduct. The locality of the induction was highly dependent on the position of the ligature. The nonligated parts of the ligated oviduct also showed a slight avidin induction. These results indicate a strictly local effect of avidin induction by ligature. An antihistamine, promethazine chloride, has a potentiating effect on the avidin induction by ligature when administered after the ligature. On the other hand, membrane stabilization by hydrocortisone or CaCl2 did not influence the ligature-induced avidin synthesis. On the basis of these results it is concluded that the avidin induction is not mediated by histamine activation or membrane damage.

Animals↗
PubMed2006

Synthesis and antitubercular activity of quaternized promazine and promethazine derivatives.

Quaternized chlorpromazine, triflupromazine, and promethazine derivatives were synthesized and examined as antitubercular agents against both actively growing and non-replicating Mycobacterium tuberculosis H37Rv. Impressively, several compounds inhibited non-replicating M. tuberculosis at concentrations equal to or double their MICs against the actively growing strain. All active compounds were non-toxic toward Vero cells (IC50 > 128 microM). N-Allylchlorpromazinium bromide was only weakly antitubercular, but replacing allyl with benzyl or substituted benzyl improved potency. An electron-withdrawing substituent on the phenothiazine ring was also essential. Branching at the carbon chain decreased antitubercular activity. The optimum antitubercular structures possessed N-(4- or 3-chlorobenzyl) substitution on triflupromazine.

Antitubercular Agents↗
PubMed2005

Hydroxyzine, promethazine and thioridazine interaction with phospholipid monomolecular layers at the air-water interface.

In this work the interaction of Hydroxyzine, Promethazine and Thioridazine with Langmuir films of dipalmitoylphosphatidylcholine (dpPC) and dipalmitoylphosphatidic acid (dpPA), is studied. Temporal variations in lateral surface pressure (pi) were measured at different initial pi (pi(i)), subphase pH and drug-concentration. Drugs with the smallest (PRO) and largest (HYD) molecular size exhibited the lowest adsorption (k(a)) and the highest desorption (k(d)) rate constant values, respectively. The affinity binding constants (K(b)) obtained in monolayers followed the same profile (K(b,PRO) < K(b,HYD) < K(b,THI)) of the egg-PC/water partition coefficients (P) determined in bilayers. The drug concentration required to reach the half-maximal Deltapi at pi(i) = 14 mN/m (K(0.5)), was very sensitive to pH. The maximal increment in pi upon drug incorporation into the monolayer (deltapi(max)) will depend on the phospholipid collapse pressure (pi(c)), the monolayers's compressibility and drug's size, shape and charge. The higher pi(c) of dpPC lead to higher pi(cut-off) values (maximal pi allowing drug penetration), if compared with dpPA. In dpPC and dpPA pi(cut-off) decreased as a function of the molecular size of the uncharged drugs. In dpPA, protonated drugs became electrostatically trapped at the monolayer surface hence drug penetration, monolayer deformation and pi increase were impaired and the correlation between pi(cut-off) and drug molecular size was lost.

1,2-Dipalmitoylphosphatidylcholine↗