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PubMed1983

Effects of L-histidine and promethazine on apomorphine and amantadine stereotypy in rats.

Pretreatment with L-histidine, a precursor of brain histamine, and promethazine, a H1 receptor blocker, failed to modify apomorphine-induced stereotyped behaviour in rats. In contrast, pretreatment with L-histidine significantly decreased the intensity of amantadine stereotypy while pretreatment with promethazine significantly increased the intensity of amantadine stereotypy in rats. The results suggest that drugs which influence central histaminergic mechanisms are effective only in modifying the stereotyped behaviour induced by the indirectly-acting DA agonist amantadine, and fail to modify the stereotyped behaviour induced by apomorphine, a directly-acting DA agonist.

Amantadine↗
PubMed1983

Clinical investigations into antidepressive mechanisms. I. Antihistaminic and cholinolytic effects: amitriptyline versus promethazine.

It is assumed that established antidepressants exert their clinical efficacy by potentiation or decrease of central noradrenergic and serotonergic neurotransmission. However, recent experimental work suggests that antihistaminic and/or cholinolytic effects may also be involved. This double-blind controlled study compared amitriptyline (catecholamine potentiating, antihistaminic, cholinolytic) with promethazine (antihistaminic, cholinolytic) in 50 severely depressed inpatients over a 30-day treatment period. Analysis of the Hamilton depression rating scale revealed significant clinical superiority of amitriptyline over promethazine in such major depressive symptoms as depressed mood, suicidal ideation, psychic anxiety, and sleep disturbances. No significant difference was evident as far as autonomous side effects were concerned. Similar results were found by analysis of the AMP rating system. It is concluded that antihistaminic or cholinolytic effects per se do not explain the antidepressants' efficacy. However, potentiation of noradrenergic neurotransmission by cholinolytic activity might be the major antidepressive mechanism.

Adult↗
PubMed1991

The effects of morphine, morphine plus scopolamine, midazolam and promethazine on cerebrospinal fluid histamine concentration and postoperative analgesic consumption.

The effects of morphine (0.14 mg/kg), morphine (0.14 mg/kg plus scopolamine (0.042 mg/kg), midazolam (0.015 mg/kg) and promethazine (0.08 mg/kg) on cerebrospinal fluid histamine (CSF-HA) and CSF-methylhistamine were investigated in 44 healthy patients. CSF-HA was determined by HPLC. CSF-HA was found to be increased after all premedications with great individual variation (range 0.07-7.4 pmol/ml). The highest values were found in the promethazine group (1.83 +/- 2.2 (SD) pmol/ml and the lowest in the control group (0.63 +/- 0.42 pmol/ml). Measurable concentrations of CSF-methylhistamine were found in 13 patients without correlation with HA. Postoperative need for analgesics was reduced in all premedicated groups. A significant correlation existed between HA and need for postoperative analgesics in the morphine plus scopolamine group. It is concluded that the histamine system plays a role in central nociception.

Adult↗
PubMed1987

Effects of Ca2+, theophylline and promethazine on protein phosphorylation in intact cells of rabbit ileum. Correlation with active Na and Cl absorption.

The effects of Ca2+, theophylline and promethazine on the phosphorylation of microvillus membrane proteins have been studied in rabbit ileal epithelial cells, using intact cell phosphorylation techniques followed by purification of microvillus membranes, separation of peptides by two-dimensional polyacrylamide gel electrophoresis, and quantitation of phosphorylation by computerized densitometry of autoradiograms. The Ca2+ ionophore A23187 caused increased phosphorylation of four and possibly five polypeptides; theophylline increased phosphorylation of three peptides, two of which had the same Mr and pI values as the peptides altered by the Ca2+ ionophore; promethazine decreased the phosphorylation of one of the peptides increased by Ca2+ ionophore. The phosphorylated peptides, which respond similarly to more than one agent which affect ileal Na and Cl absorption, could be involved in the regulation of NaCl absorption either as transport proteins or regulators of transport proteins.

Animals↗
PubMed1993

Kinetic fluorimetric determination of promethazine by a stopped-flow mixing technique.

The oxidation of promethazine to its corresponding fluorescent sulphoxide was used to develop a novel kinetic fluorimetric method for the determination of this drug. The use of a stopped-flow mixing technique makes use of an oxidizing reagent unnecessary because the oxidation is rapidly carried out by dissolved oxygen. The method is simple and fast as it only requires a few seconds to obtain kinetic data which allows ready application to routine analyses. The calibration graph is linear over the range 0.5-80 micrograms ml-1 and the precision (%RSD) is close to 2%. The method was applied to the determination of promethazine hydrochloride in two pharmaceutical preparations.

Chemistry, Pharmaceutical↗
PubMed1995

A liquid chromatographic method for the determination of promethazine enantiomers in human urine and serum using solid-phase extraction and fluorescence detection.

A LC method was developed for the concurrent assay of R(+) and S(-) promethazine from human urine and serum. The method involves the use of solid-phase extraction for sample clean-up. Chromatographic resolution of the enantiomers was performed under isocratic conditions using a mobile phase of hexane-1,2-dichlorethane-absolute ethanol-trifluoroacetic acid (400:150:100:1, v/v/v/v) at a flow rate of 1 ml min-1 on a brush-type column KK-CARNU. The enantiomers were detected by fluorescence using an excitation wavelength of 250 nm and a 280 nm emission cutoff filter. Chlorpromazine was used as the internal standard for urine analysis. Standard addition was used for promethazine analysis from serum. Drug to internal standard ratios were linear from 0.25 to 10 micrograms ml-1 in urine. Serum levels were linear from 2 to 10 ng ml-1.

Chlorpromazine↗
PubMed2005

Determination of promethazine hydrochloride and its preparations by highly accurate nephelometric titration.

A highly accurate nephelometric titration for the determination of promethazine hydrochloride and its preparations was presented. The titration operating conditions were studied and the solubility product constant of promethazine tetraphenylboron precipitation was determined. The result of the titration is comparable to those of control experiments. The proposed method has been found to be accurate, precise, specific and linear.

Nephelometry and Turbidimetry↗
PubMed2004

Bead injection spectroscopy-flow injection analysis (BIS-FIA): an interesting tool applicable to pharmaceutical analysis. Determination of promethazine and trifluoperazine.

A bead injection spectroscopy-flow injection analysis (BIS-FIA) system for the spectrophotometric detection of promethazine and trifluoperazine is developed. The sensor is based in the oxidation of the phenothiazines by Fe(III) which is later determined by formation of the complex between Fe(II) and Ferrozine, [FeFz(3)](4-). Immediately, this complex is retained on a homogeneous bead suspension of Sephadex QAE A-25 resin (500 microl) which has been injected previously in the system to fill a commercial flow-cell (Hellma 138-OS). The use of BI with respect to the use of a reusable flow-through sensor is justified because the complex is so strongly retained on the beads that the regeneration of the solid support becomes extraordinarily difficult in the proposed method. At the end of the analysis, beads are automatically discarded from the flow-cell, by reversing the flow, and transported out of the system. The analytical signals are measured at a wavelength of 567 nm, corresponding to the absorbance of the complex. Using a sample volume of 600 microl, the analytical signal showed a very good linearity in the range 0.5-8.0 microgml(-1) and 0.5-10.0 microgml(-1), with detection limits of 0.09 and 0.14 microgml(-1) for promethazine and trifluoperazine, respectively. R.S.D.s (%) lower than 2% were obtained for both analytes. The proposed method is highly selective in the presence of other species that are normally encountered with these analytes. The sensor was satisfactorily applied to pharmaceutical preparations.

Dosage Forms↗
PubMed2005

The human Ca2+-activated K+ channel, IK, can be blocked by the tricyclic antihistamine promethazine.

Phenothiazines can be used as psychopharmaceutical agents and are known to cause many side effects during treatment since they interfere with many different cellular systems. Recently, phenothiazines were reported to block Ca(2+)-activated potassium channels of the SK type. Therefore we investigated their effect on the functionally related class of Ca(2+)-activated potassium channels of the IK type. The representative phenothiazine derivative promethazine (PTZ) blocked IK channels almost independently from the extracellular pH(o) with an IC(50) of 49 +/- 0.2 microM (pH(o) 7.4, n = 5) and 32 +/- 0.2 microM (pH(o) 6.2, n = 5) in whole cell experiments. The extracellularly applied membrane impermeable PTZ analogue methyl-promethazine (M-PTZ) had a strongly reduced blocking potency compared to PTZ. In contrast, intracellularly applied PTZ and M-PTZ had the same blocking potency on IK channels in excised inside out patch clamp experiments (K(d) = 9.3 +/- 0.5 microM for PTZ, n = 7 and 6.7 +/- 0.4 microM for M-PTZ, n = 5). The voltage dependency of the PTZ and M-PTZ block was investigated in excised inside out patch clamp experiments at a concentration of 100 microM. For both compounds the block was more pronounced at positive membrane potentials. The steepness of the voltage dependency was found to be 70 +/- 10 mV (for PTZ) and 61 +/- 6 mV (for M-PTZ) indicating that both compounds sensed approximately 40% of the entire membrane spanning electrical field from the inside. We conclude that PTZ and M-PTZ bind to a side in IK channels, which is located within the electrical field and is accessible from the intracellular side.

Calcium↗
PubMed1976

Possible effect of maternal promethazine therapy on neonatal immunologic functions.

The effect of the administration of promethazine in the treatment of erythroblastosis fetalis was studied in four maternal-fetal pairs. The three infants exposed for a prolonged period of time had decreased neonatal number and function of T cells, and abnormal specific humoral immune responses. The possible role of promethazine in the induction of fetal immunoincompetence is discussed.

Antibodies↗
PubMed1993

Comparison of intramuscular meperidine and promethazine with and without chlorpromazine: a randomized, prospective, double-blind trial.

STUDY OBJECTIVES: To compare the effectiveness of intramuscular meperidine (2 mg/kg) and promethazine (1 mg/kg) with chlorpromazine (MPC) or without chlorpromazine (MP) (1 mg/kg) for sedation of children undergoing emergency department procedures. DESIGN: Randomized, double-blind trial. SETTING: A community and university hospital ED. TYPE OF PARTICIPANTS: Eighty-seven hemodynamically and neurologically stable children less than 16 years old. INTERVENTIONS: IM sedation followed by intended procedure. MEASUREMENTS AND MAIN RESULTS: Children receiving either combination were not significantly different with regard to age, sex, weight, chronic illness, and indications. Procedures included laceration repair (46), fracture reduction (25), and others (16). Mean onset of action was similar (16 +/- 12 minutes), whereas the duration of action was significantly longer after MPC (63 +/- 57 minutes [mean +/- SD] compared with MP 29 +/- 36 minutes; P < .05, Student's t-test). Paradoxical hyperactivity occurred only after MP (three of 43 cases; P = NS, Fisher's exact test), whereas transient oxygen desaturation occurred only after MPC (one of 44 cases; P = NS). No other serious complications were observed. Three observers rated the effectiveness of sedation and analgesia on separate 10.2-cm visual-analog scales. Overall, MPC received significantly better ratings (7.4 +/- 2.1 cm) than MP (5.7 +/- 3.0 cm; P < .05, Mann-Whitney U test). Parents believed sedation worked well in 90% of cases. Their children had bad memories of the procedure in only 9% of cases. CONCLUSION: Elimination of chlorpromazine from the IM combination of meperidine and promethazine for pediatric sedation during ED procedures results in a significant reduction in efficacy.

Adolescent↗
PubMed1996

Comparison of oral transmucosal fentanyl citrate and intramuscular meperidine, promethazine, and chlorpromazine for conscious sedation of children undergoing laceration repair.

STUDY OBJECTIVE: To compare oral transmucosal fentanyl citrate (OTFC) with IM meperidine, promethazine, and chlorpromazine (MPC) for conscious sedation of children. METHODS: This prospective, randomized, single-blinded study involved a convenience sample of 40 children, 3 to 8 years of age, who presented to an urban pediatric emergency department and required laceration repair. Patients were premedicated with either OTFC (10 to 15 micrograms/kg) and a mock injection or intramuscular MPC (2 mg/kg meperidine, .5 mg/kg promethazine, and .5 mg/kg chlorpromazine) followed by a placebo lozenge. RESULTS: Both OTFC and MPC caused significant reductions in activity scores at 15 to 75 minutes after medication administration. Although the MPC group was more sedated, there was no difference between groups in Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores during the laceration repair or in the suturing physician's assessment of sedation quality (rated excellent or good for 75% and 69% of OTFC and MPC groups, respectively). Two children (both in the OTFC group) had oxygen saturation levels of less than 95% but required only transient supplemental oxygen. Other adverse events were common but not serious; they differed between groups in type but not number, with vomiting in 45% of the OTFC group and prolonged somnolence in 37% of the MPC group. Mean time to discharge was 99 minutes, with no difference between groups. CONCLUSIONS: Both medications reduced activity significantly. Although MPC caused deeper sedation, the medications had comparable effects on patient behavior during the repair and yielded comparable ratings of physician satisfaction. Large numbers of nonserious adverse events occurred in both groups.

Administration, Oral↗
PubMed1996

Successful cancer therapy with promethazine: the rationale.

Evidence supporting the claim that specific phenothiazines, notably chlorpromazine and promethazine, may be used as sole agents for the treatment of cancer in man, has been reviewed. Selective destruction of cancerous tissue can be achieved by modulating energy metabolism in malignant cells. In the light of available information, the drug of choice is promethazine, the effects of which on the central nervous system are relatively weak. The maintenance of continuous pharmacological pressure against malignant growths forms an essential feature of the therapy. Protection against blood dyscrasias may be secured through the provision of adequate amounts of trace elements necessary for the function of enzyme systems which detoxicate active oxygen species. Tumour-cell death may be facilitated by nutritional supplements of specific polyunsaturated fatty acids. Interference from adventitious medications and drug resistance are discussed; appropriate therapy is outlined.

Antineoplastic Agents↗
PubMed1999

Separation of promethazine and thioridazine using capillary electrophoresis with end-column amperometric detection.

Promethazine and thioridazine were separated and detected by capillary electrophoresis with end-column amperometric detection. The influence of pH value on oxidation potential, the peak current and the resolution were studied and the following conditions was selected: 0.03 M Na2HPO4 and 0.015 M citric acid at pH 3.0, detection potential at 1.10 V. The detection limits of these two substances were in the range of 10(-8) mol/l. The linear range spanned two to three orders of magnitude. This method was applied to the detection of promethazine and thioridazine spiked in urine.

Antipsychotic Agents↗
PubMed1997

Quantitation of promethazine enantiomers in human serum using a chiralcel OJ-R column and mixed-mode disc solid-phase extraction.

A liquid chromatographic method was developed for the assay of R(+)- and S(-)-promethazine enantiomers from human serum. The method involves the use of the mixed mode disc solid-phase extraction technique for sample clean-up. Chromatographic resolution of the enantiomers was performed on a reversed-phase cellulose-based chiral column (Chiralcel OJ-R) under isocratic conditions using a mobile phase consisting of 0.5 M aqueous sodium perchlorate/acetonitrile (63:37, v/v) at a flow rate of 0.5 ml min-1. Recoveries in the range of 97-99% at 20 ng ml-1 levels were obtained for both promethazine enantiomers. Intra-day and inter-day precision calculated as R.S.D.% was in the 3-8% ranges for both enantiomers. Intra-day and inter-day accuracy calculated as percent error was in the 0-10 and 1-7% ranges for both enantiomers, respectively. Linear calibration curves were obtained for each enantiomer in serum in the concentration range 5-90 ng ml-1. The limit of quantitation of each enantiomer was 10 ng ml-1. The detection limit for each enantiomer in serum using UV detection at 249 nm was 2 ng ml-1 (S/N = 2).

Anti-Allergic Agents↗
PubMed1976

[Allergic agranulocytosis due to promethazine].

An allergic agranulocytosis developed after promethazine administration to a 34-year-old man with a compulsion neurosis. Promethazine-specific leucocyte antibodies were demonstrated in the antiglobulin consumption test. Four similar cases, reported in the literature, are discussed in relation to this personal case. The findings are contrasted to the majority of cases of toxic "phenothiazine agranulocytosis".

Adult↗
PubMed1999

Neuroleptic malignant syndrome due to promethazine.

A 42-year-old man came to our emergency room hyperthermic (oral temperature, 42.4 degrees C), diaphoretic, and delirious. Other findings included labile blood pressure, sinus tachycardia (heart rate, 138/min), tachypnea (respiratory rate 34/min), muscle rigidity, and incontinence. Two days earlier, he had gone to a local clinic with complaints of abdominal pain, nausea, and vomiting. Promethazine was prescribed, and this was the patient's only medication on admission. Laboratory studies showed leukocytosis, hypernatremia, metabolic acidosis, elevated creatinine phosphokinase level, elevated transaminase levels, azotemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and myoglobulinuria. The clinical and laboratory findings were characteristic of the neuroleptic malignant syndrome, with promethazine as the offending agent.

Acidosis↗
PubMed1980

A sex difference in the effects of oral codeine and promethazine on the ventilatory response to carbon dioxide in human volunteers.

1 Interactions between codeine and promethazine have been studied in male and female volunteers, measuring ventilation, end tidal PCO2, ventilatory response to CO2, pulse and blood pressure. 2 The effects of codeine on the above measurements have been compared in subjects who habitually smoke cigarettes and non smoking subjects. 3 Codeine displaced the ventilatory response to CO2 to the right and increased end tidal PCO2 in female subjects but not in males. 4 Promethazine plus codeine displaced the ventilatory response to CO2 to the right in male subjects but tended to reduce the response to codeine in females. 5 The slope of the ventilatory response to CO2 was significantly steeper in smokers and codeine caused significant reductions in slope in these subjects.

Adult↗