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PubMed1995

Comparison of dihydroergotamine with metoclopramide versus meperidine with promethazine in the treatment of acute migraine.

Migraineurs often seek office-based treatment for acute headache. To compare the efficacy and side effect profile, we entered 27 migraineurs into a prospective, randomized, double-blind study where each patient received either 75 mg meperidine with 25 mg promethazine IM or .5 mg dihydroergotamine with 10 mg metoclopramide IV. After 1 hour, pain relief was similar in the two groups, but side effects were significantly greater in the meperidine with promethazine regimen group. The dihydroergotamine with metoclopramide regimen is effective, and has minimal side effects, making it an attractive method for office-based treatment of acute migraine.

Acute Disease↗
PubMed1983

Oral promethazine hydrochloride in ethylenediamine-sensitive patients.

A study of 12 patients with allergic contact sensitivity to ethylenediamine has shown that exposure to the oral antihistamine promethazine hydrochloride (Phenergan) did not result in an exacerbation or recrudescence of eczema. This would suggest that promethazine may be safely administered to ethylenediamine-sensitive patients contrary to advice given in some of the dermatological literature.

Administration, Oral↗
PubMed1973

Effects of promethazine-hydrochloride on human polymorphonuclear leukocytes.

Promethazine hydrochloride at a concentration of 0.033 mg/ml has pronounced effects on leukocyte metabolism and function. The drug inhibits the phagocytosis-induced increases in O(2) consumption and hexose monophosphate shunt activity. Associated with these effects is an inhibition of the iodination of zymosan particles and an inhibition of bacterial killing by the cell. At least two mechanisms appear to be involved. Many of the effects can be explained by an inhibition of phagocytosis, but promethazine also inhibits the decarboxylation of amino acids and iodide fixation in a cell-free system, indicating a specific effect on metabolism. These results may partially account for the action of the drug in ameliorating the effects of erythroblastosis.

Cell Nucleus↗
PubMed1977

Selective inhibition of Bacillus subtilis sporulation by acridine orange and promethazine.

Two structurally similar compounds were found to inhibit sporulation in Bacillus subtilis 168. A dye, acridine orange, and an antischizophrenic drug, promethazine, blocked spore formation at concentrations subinhibitory to vegetative growth, while allowing synthesis of serine protease, antibiotic, and certain catabolite-repressed enzymes. The sporulation process was sensitive to promethazine through T2, whereas acridine orange was inhibitory until T4. The drug-treated cells were able to support the replication of phages phie and phi29, although the lytic cycles were altered slightly. The selective inhibition of sporulation by these compounds may be related to the affinity of some sporulation-specific genes to intercalating compounds.

Acridines↗
PubMed1985

Promethazine or DPPD pretreatment attenuates oleic acid-induced injury in isolated canine lungs.

Oleic acid causes pulmonary edema by increasing capillary endothelial permeability, although the mechanism of this action is uncertain. We tested the hypothesis that the damage is an oxidant injury initiated by oleic acid, using isolated blood-perfused canine lung lobes. The lobes were dilated with papaverine and perfused in zone III with a constant airway pressure of 3 cmH2O. Changes in isogravimetric capillary pressure (Pc,i) and capillary filtration coefficient (Kf,C) were used as indices of alterations in microvascular permeability in lungs treated with silicone fluid (n = 3), oleic acid (n = 11), oleic acid after pretreatment with the antioxidants promethazine HCl (n = 11) or N,N'-diphenyl-p-phenylenediamine (DPPD; n = 4), or oleic acid following pretreatment with methylprednisolone (n = 4). Kf,C averaged 0.21 +/- 0.02 ml X min-1 X cmH2O-1 X 100 g-1 in control and increased to 0.55 +/- 0.05 and 0.47 +/- 0.05 when measured 20 and 180 min after the administration of oleic acid. When oleic acid was infused into lungs pretreated with promethazine, Kf,C increased to only 0.38 +/- 0.05 ml X min-1 X cmH2O-1 X 100 g-1 after 20 min and had returned to control levels by 180 min. Pretreatment with DPPD, but not methylprednisolone, similarly attenuated the increase in Kf,C following oleic acid. Silicone fluid had no effect on Kf,C. That oleic acid increases vascular permeability was also evidenced by a fall (P less than 0.05) in Pc,i from control when measured at 180 min in every group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

Butorphanol and promethazine as pre-anaesthetic medication.

An open evaluation of a combination of butorphanol (1 or 2 mg), promethazine (25 or 50 mg) and atropine (0.5 mg) in 109 adult consenting patients was carried out to determine their safety and efficacy for preanaesthetic medication. All patients were kept under direct surveillance from before intramuscular medication until they were in satisfactory condition post-operatively for discharge from the recovery room. The medications employed did not disturb the blood pressure, pulse rate or respiration rate in any of the patients. None complained of nausea or dizziness while only one was slightly excited. Sedation was rated as satisfactory in 97 per cent, and 90 per cent were free of apprehension. In addition, global evaluation of the premedication by the investigator was rated good to excellent in 99 per cent of the patients. On the basis of these observations, the combination of butorphanol with promethazine and atropine appears safe and useful for pre-anaesthetic medication.

Adolescent↗
PubMed1976

The effect of promethazine hydrochloride on bilirubin metabolism in the rat.

The effect of 21 days of promethazine-HC1 administration on hepatic bilirubin metabolism and transport was studied in adult rats. A significant increase in mean cumulative hepatic bilirubin uptake (84.5 +/- 7.6 (SE) mug/100 g/min in controls vs. 110.0 +/- 4.3 in treated rats), mean hepatic glucuronide conjugation (1,330 +/- 86 (SE) mug bilirubin conjugated/g liver/40 min in controls vs. 1.713 +/- 61 in treated rats), and mean maximal hepatic excretion (47.2 +/- 4.9 (SE) mug/100 g/min vs. 63.5 +/- 2.7) was observed in treated animals. Mean total liver weight and total hepatic protein also increased significantly. These observations suggest that promethazine is an inducer of protein and enzyme synthesis in rat liver and is capable of significantly stimulating the three major steps in hepatic disposal of bilirubin.

Animals↗
PubMed2005

Determination of promethazine hydrochloride in pharmaceuticals by capillary isotachophoresis.

Capillary isotachophoresis (ITP) in cationic regime of the separation with conductometric detection has been used for the separation and determination of promethazine hydrochloride (PRO) in commercial mass-produced pharmaceutical preparations. Several electrolyte systems of different compositions and pH were examined and the optimized ITP electrolyte system consisted of 10 mmol/l of potassium acetate adjusted to pH 4.8 with acetic acid as the leading electrolyte with electroosmotic flow (EOF) suppressing additive, 0.2% (w/v) methylhydroxyethylcellulose (m-HEC), and 5 mmol/l of beta-alanine as the terminating electrolyte. The proposed electrophoretic method was successfully validated. It was convenient for the sensitive, simple, rapid, and highly reproducible assay of promethazine. The calibration graph relating the ITP zone length to concentration of the analyte was rectilinear in the range of 40-200 mg/l of the drug standard, with a coefficient of determination r(2)=0.9992. The relative standard deviation (RSD) was 1.12% (n=6) when determining 100 mg/l of PRO in standard sample. Good quantitation was obtained in short analysis time (a single analysis took 6 min). The recoveries of drug from samples were found to be 97.22% (tablets), 99.72% (injections), and 99.14% (syrup). The minimal sample pretreatment and low running cost make the proposed ITP method a good alternative to commonly used analytical methods.

Electrophoresis, Capillary↗
PubMed1981

Metabolism of promethazine in vitro. Identificaton of N-oxidized products.

1. Incubation of promethazine (Ia) and desmethylpromethazine (Ib) with 9000g supernatant fractions of rabbit liver homogenate resulted in formation of N-dealkylated, N-oxygenated and ring-hydroxylated products. 2. The N-oxidation products identified by t.l.c. and mass spectra using synthetic reference products are promethazine-N-oxide (IX) and the nitrone (VIII), which is believed to be formed chemically and metabolically from the metabolite N-hydroxydesmethylpromethazine (VII).

Animals↗
PubMed1998

Bioinorganic study on [Fe(promethazine)2H2O Cl]2+ complex.

The coordination chemistry of iron (III) is the environment of an antihistaminic drug, promethazine has been explained to include a low spin, six-coordinate complex [Fe(Prometha)2(H2O) Cl] Cl2. Metaldrug interaction in vitro in aqueous KCl phase was studied polarographically at physiological pH and temperature. On the basis of elemental, magnetic, conductometric, IR, UV-visible, NMR spectroscopic analysis it is concluded that in solid phase two promethazine molecules with their N,N donor sites encompass the metal. Mass spectral study on the complex confirms that one of the three chlorides is involved in the coordination. The respective changes in the antihistaminic activity of the drug as a result of complexation has been determined and a possible mechanism is suggested.

Animals↗
PubMed1998

Effects of trifluoperazine and promethazine on the release of transmitter quanta at the mouse neuromuscular junction.

The present experiments examined the effects of phenothiazine derivatives, such as trifluoperazine and promethazine, on the release of transmitter quanta in preparations of the mouse diaphragm. The frequency (F, s-1) of miniature end-plate potentials and the quantal content (m) of endplate potentials were measured intracellularly at the same endplate in a bathing solution that contained 0.5-0.8 mM Ca2+ ions and 5 mM Mg2+ ions. Trifluoperazine (4 microM) significantly reduced both F and m. The inhibitory effect on m, but not on F, was subject to competition by Ca2+ ions. Promethazine at 48 microM, but not at 16 microM, reduced the quantal release. It was apparent that the effect of trifluoperazine was competitively antagonized by Ca2+ ions at motor nerve terminals.

Animals↗
PubMedDate not supplied

Comparing the safety, efficacy and recovery of intranasal midazolam vs. oral chloral hydrate and promethazine.

PURPOSE: The purpose of this study was to compare the safety, efficacy and recovery time of intranasal midazolam spray administered using an atomizer to orally administered chloral hydrate and promethazine for the sedation of pediatric dental patients. METHODS: A randomized double-blind crossover study design was utilized in which 31 patients (mean age 41.8 months, range 26-58 months) underwent two restorative dental appointments. At one appointment, subjects received 0.2 mg/kg intranasal midazolam; at the other appointment subjects received 62.5 mg/kg chloral hydrate with 12.5 mg promethazine. Administered at each appointment was 25%-50% N(2)0/0(2). Physiologic parameters (heart rate, blood pressure, respiratory rate, oxygen saturation) and behavior assessments (crying, movement, sleep) using the Houpt Sedation Rating Scale were recorded at baseline and every five minutes during treatment. Overall behavior was assessed at baseline and at the end of treatment. Following treatment, a modified Vancouver Recovery Scale was used to determine the length of time it took each subject to meet established discharge criteria. RESULTS: There were no clinically significant differences in physiologic parameters, however a statistically significant decrease in systolic and diastolic blood pressure was observed in patients sedated with chloral hydrate/promethazine. There were no significant differences in behavior between groups. Patients sedated with intranasal midazolam slept less and recovered quicker than patients sedated with oral chloral hydrate/promethazine. CONCLUSIONS: Intranasal midazolam administered using an atomizer is as safe (as assessed by physiologic parameters) and effective (as assessed by behavior ratings) as oral chloral hydrate/promethazine for conscious sedation of pediatric dental patients.

Administration, Inhalation↗
PubMed2004

Plasmodium berghei: efficacy and safety of combinations of chloroquine and promethazine in chloroquine resistant infections in gravid mice.

Efficacy and safety of combinations ofChloroquine (CQ) and doses of Promethazine (PR) against CQ resistant Plasmodium berghei infections in gravid mice was evaluated. Parasites were cleared faster in mice treated with CQ combined with doses of PR ranging from 20mg/kg to 50mg/kg (3.4 +/- 0.5 to 2.7 +/- 0.7) compared with CQ alone (4.7 +/- 0.8) (P<0.5). Parturition resulting in live pups in animals treated with CQ and 20mg/ kg and 30mg/kg of PR (81%) was significantly higher than in animals treated with CQ alone (44%) or saline (13%). Mean birth weight of pups delivered by infected gravid animals treated with CQ and 30mg/kg or 40mg/kg of PR (1.51 +/- 0.16 or 1.56 +/- 0.16) was significantly higher than animals treated with CQ alone (1.33 +/- 0.13) (P=0.00004, 0.0014 respectively). No gross malformations were observed in pups delivered by infected or non-infected animals treated with the combinations of chloroquine and Promethazine.

Animals↗
PubMed1985

Stability of meperidine hydrochloride, promethazine hydrochloride, and atropine sulfate in plastic syringes.

The stability of a combination of meperidine hydrochloride 50 mg, promethazine hydrochloride 25 mg, and atropine sulfate 0.4 mg in plastic syringes at room temperature was studied. The samples were tested for each drug after 0.5, 1, 3, 6, and 24 hours in the syringes. Freshly prepared mixtures of the drugs in glass containers were used as controls, and three trials using separate test mixtures were performed. A gas chromatography procedure was used; atropine was separated from the mixture and assayed alone for greater accuracy. Drug concentrations in the plastic syringes were not significantly different from controls at any of the test times. A mixture of meperidine hydrochloride, promethazine hydrochloride, and atropine sulfate in dosages commonly administered as a preoperative medication was stable for 24 hours in plastic syringes.

Atropine↗
PubMed1979

Control of radiation-induced emesis with promethazine, cimetidine, thiethylperazine, or naloxone.

Promethazine (2 mg/kg), cimetidine (4 mg/kg), thiethylperazine (0.86 mg/kg), and naloxone (0.08 mg/kg) were each evaluated for their ability to increase the threshold of radiation-induced emesis in the dog. Each dog was fed a can of dog food (ca 0.4 kg) and then injected IM with the appropriate drug 1 hour before being irradiated by a 60Co teletherapy unit. The total radiation dose given an individual dog was determined by an up-and-down exposure schedule. Dogs were then observed continuously for 10 hours while the number, time of onset, and duration of each emetic episode were monitored. The dose of radiation causing emesis in 50% (ED50 +/- SEM) of control dogs was 170 +/- 38.5 rad. The ED50 +/- SEM was increased to 402 +/- 18.6 rad by promethazine, to 331 +/- 27.3 rad by cimetidine, and to 320 +/- 38.5 rad by thiethylperazine. This increased tolerance was significant at P less than 0.05 for each drug. The ED50 for naloxone was 262.5 +/- 92.9 rad, which was not a statistically significant increase in threshold.

Animals↗
PubMed1983

Whole body distribution of the quaternary ammonium compound thiazinamium (N-methylpromethazine) and promethazine in monkey and mice.

The distribution of 35S-ringlabeled thiazinamium (N-methyl-promethazine) methylsulphate (35S-Th.) and its tertiary analog 35S-promethazine hydrochloride (35S-Pr.) have been studied by means of whole body autoradiography in a squirrel monkey and in mice. After infusion of 35S-Th. in the monkey until steady state condition, high accumulations of radioactivity were found in the three main organs of excretion of the drug (liver, kidneys and intestines). High concentrations of radioactivity were also observed in organs with high amounts of acetylcholine receptor such as the ganglia, skeletal muscles, myocard and ciliary bodies, and in glandular tissue such as salivary glands, thyroid gland and pancreas. On the other hand no radioactivity was seen in the central nervous system with exception of the posterior pituitary gland and the fourth ventricle. This suggests that Th.-cations cannot pass "the blood-brain barrier", except for some high permeability regions that are known to be "windows" in this barrier. 35S-Pr. was distributed significantly different. Now a high level of radioactivity was seen in the central nervous system, indicating that the tertiary amine compound can easily pass "the blood-brain barrier". Again high concentrations of radiation were found in liver, kidneys and intestines. 35S-Pr. also seemed to penetrate to acetylcholine receptor areas. Substantial accumulation in the eye was seen, as well as in glandular tissues. Essentially the same distribution patterns as described above were seen for 35S-Th. and 35S-Pr. after intramuscular injection in mice. In pregnant mice, after administration of 35S-Th. high concentration of radioactivity was found in the placenta, but only low amounts were seen in the foetus, and then only in the liver and the kidneys, which implies that Th.-cations can pass the placenta, however, to a low extent and at a low rate. With 35S-Pr. obviously placenta transfer can occur more easily and distribution in the foetus is not restricted to the liver and kidneys.

Animals↗
PubMed1978

In vitro and in vivo effects of promethazine (Phenergan) on drug metabolism.

Prolongation effects of promethazine on the pentobarbital sleeping time are not due to interactions of this drug with cytochrome P-450 or cytochrome c reductase or inhibition of drug metabolism because pentobarbital plasma levels in promethazine treated animals before awakening are not different than in controls. Results suggest additive effects of both drugs on the central nervous system. Those interactions do however play a role during in vitro studies.

Animals↗
PubMed1983

[Premedication with flunitrazepam, lormetazepam or pethidine-promethazine. Psychometric study of subjective conditions].

In the course of a clinical study oral administration of two different diazepine derivatives as well as i.m. injection of pethidine and promethazine have been explored with a view to their anxiolytic, sedating and hypnotic action. The study involved 128 patients, randomized into four groups. Group 1 received flunitrazepam 1,5-2 mg p.o. only the evening before operation to group 2 flunitrazepam 1,5-2 p.o. was administered the evening before and the morning of the operation, group 3 were given lormetazepam 2-2,5 mg p.o. at the same time as group 2, in group 4 nitrazepam, 5 mg p.o. the evening before operation and pethidine, 50-100 mg combined with promethazine, 25 mg was given i.m. 60 min before surgery. In group 1 anxiolytic and sedating effect of flunitrazepam were not persistent enough to provide the patient with adequate premedication until the onset of surgery. Intensive sedation and fatigue as well as minimum recollection were observed under medication 2, however, increase in anxiety and depression as well as deterioration of mood were not prevented. Under medication 3 patients felt less exhausted and fatigued than under medication 2, but likewise anxiety and depression increased in the course of the operating day. Group 4 emerged as the last effective premedication both with regard to sleep during the previous night and the conditions of the day of the operation itself.

Adult↗