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PubMedDate not supplied

Spectrofluorometric determination of 2- and 10-disubstituted phenothiazines.

Spectrofluorometric method for determination of promethazine hydrochloride, thioridazine hydrochloride and perazine dimaleate in the pure form and in drugs is described. Fluorescence excitation spectra of series of aqueous solutions were measured. The fluorescence signal was found to be a linear function of the promethazine hydrochloride (PTM) concentration in the range: 0.30-20.02 ppm, thioridazine hydrochloride (TR): (0.43-21.70 ppm and perazine dimaleate (PDM): 0.85-50.60 ppm. The excitation spectra were used for determination of phenothiazine derivatives in pharmaceutical formulations such as: Diphergan, Thioridazin and Pernazinum. The influence of K+, Na+, Mg2+ i Ca2+ cations on the fluorescence intensity of phenothiazine derivatives was also studied.

Antipsychotic Agents↗
PubMed2001

Antihypertensive therapy in critical occupations: studies with an angiotensin II antagonist.

OBJECTIVE: This study was performed to establish whether an angiotensin II antagonist modulates daytime sleepiness or performance. METHODS: The central effects of losartan (50 and 100 mg), as well as amlodipine (5 and 10 mg) and promethazine (10 mg), were studied in six healthy volunteers (aged between 20 and 27 (mean 24) yr). Digit symbol substitution, tracking, vigilance, immediate and short-term memory recall, complex reaction time, together with objective (daytime sleep latencies) and subjective measures of sleepiness, were measured 1.0 h before and 0.5, 2.0, 3.5, 5.0, 6.5, and 8.0 h after ingestion. The study was placebo-controlled and double-blind with a six-way crossover design. RESULTS: No changes in performance or in measurements related to sleepiness were observed with losartan (50 and 100 mg). Amlodipine (10 mg) impaired immediate memory and increased subjective sleepiness at 8.0 h (p < 0.05). Promethazine (10 mg) impaired vigilance and immediate memory recall and increased reaction time (basic and complex) from 2.0 to 6.5 h after ingestion, impaired tracking from 3.5 to 6.5 h and increased subjective sleepiness from 2.0 to 8.0 h (p < 0.05). CONCLUSION: The study suggests that an angiotensin II antagonist could prove useful for the treatment of hypertension in aircrew.

Adult↗
PubMed2002

[A case of fluvoxamine overdose].

Selective serotonin reuptake inhibitors (SSRI) are newly developed-antidepressants authorized in 1999 in Japan. We experienced a case of drug poisoning including fluvoxamine, one of SSRI. A comatose nineteen-year-old girl was transported to our ER in the morning on July 25, 2000. There remained many empty packages of fluvoxamine and several sorts of tranquilizers in the room. Her consciousness became alert over the next morning. HPLC analysis revealed fluvoxamine, chlorpromazine, promethazine, biperiden, phenobarbital, and zopiclone in her blood and that serum concentrations of the first three were above the therapeutic ranges. The peak values of fluvoxamine, chlorpromazine, and promethazine were 1,343 ng/ml (6.7 times of the upper limit), 861 ng/ml (2 times), and 529 ng/ml (1.3 times), respectively. Fluvoxamine must be a main cause of her toxic symptoms although other CNS-depressing drugs might work jointly.

Adult↗
PubMed1992

On the value of giving a combination of drugs for the treatment of endotoxaemia in pigs.

OBJECTIVE: To see if treatment with a combination of drugs each directed at a different mediator was successful in preventing activation of those mediators in experimental endotoxic shock. DESIGN: Controlled study. MATERIAL: 40 juvenile pigs. INTERVENTIONS: 33 animals received 0.01 mg/kg endotoxin infusion, the rest being given the same volume of saline; 10 of the 33 received no treatment. Of the remaining 23, 5 were given combination treatment with methylprednisolone, naloxone, ketanserin, promethazine, C1 esterase inhibitor, antithrombin III and aprotinin; 7 were given methylprednisolone only; 6 were given the three protease inhibitors (C1 esterase inhibitor, antithrombin III and aprotinin); and 5 were given naloxone, ketanserin and promethazine. MAIN OUTCOME MEASURES: Assessment of haemodynamic, proteolytic, and cellular effects of endotoxaemia. RESULTS: Only the combination treatment totally blocked all the effects of the infusion of endotoxin. CONCLUSION: As endotoxin affects several mediators, combination treatment is necessary to block all its deleterious effects in pigs.

Animals↗
PubMed1992

Maternal immunity to red cell antigens and fetal transfusion.

This article has presented an overview of developments in the treatment of HDN. The number of cases requiring treatment that have occurred in the last decade has dropped because of the development and implementation of Rh immunoprophylaxis, although this treatment still appears to be underutilized in the United States. Failure to recognize the need for immunoprophylaxis in certain situations (including unrecognized abortion) has led to a small residual population of alloimmunized mothers who will require comprehensive treatment during subsequent pregnancies. Alloimmunization to other red cell antigens remains a small but significant problem in other women. Although great advances have been made in the monitoring of these pregnancies, amniotic fluid analysis remains a mainstay for the third-trimester evaluation of alloimmunized pregnancies. Noninvasive methods such as ultrasound evaluation and the monocyte assays may supplement, but cannot entirely replace, the need for direct assessment. The most striking advancement in the evaluation and treatment of these infants has been the ability to access the fetal circulation directly through intravenous umbilical cord sampling. This method allows for an immediate assessment of fetal anemia as well as a route for direct fetal transfusion. The method has also permitted a more complete assessment of fetal physiology. However, the method may be overutilized at the present time and has some degree of risk to the fetus, even in experienced hands. Additional methods of treatment for the alloimmunized pregnancy include plasma exchange, intravenous immunoglobulin infusion, and promethazine hydrochloride. The popularity of plasma exchange has probably decreased with the advent of more direct fetal sampling and treatment techniques, but it may be useful in the treatment of first-trimester pregnancy losses. Intravenous immunoglobulin and promethazine hydrochloride appear to be promising alternatives that require more investigation. It is apparent that efforts need to be channeled towards prevention of HDN in a health system that is highly aware of increasing costs and the benefits of preventive medicine.

Blood Transfusion, Intrauterine↗
PubMed2004

Cardiovascular changes during halothane induction in children.

OBJECTIVES: The incidence of bradycardia and myocardial depression following halothane induction in children is well documented. Bradycardia leads to reduced cardiac output, which can result in compromised organ perfusion. Halothane may sometimes induce arrhythmia. There is at present no study in this sub-region on the cardiovascular changes of halothane induction in children. This study was designed to investigate the cardiovascular changes and incidence of arrhythmias following halothane induction. PATIENTS AND METHODS: Ninety ASA I - II children aged 6 months to 12 years were studied. Premedication with oral promethazine 1mg/kg was given to all patients above the age of one year. Anaesthesia was achieved with incremental halothane up to 3% in 33% oxygen and nitrous oxide. Halothane induction led to a significant drop in SBP, DBP and MAP in all patients at the end of induction. (p < 0.005). Heart rate values were significantly less postinduction in children older than one year (p < 0.05). Arrhythmias occurred in 3.3% of all patients. No patient experienced bradycardia. Other complications included hypotension (8.8% ) and mild laryngeal spasm (2.2% ). RESULTS: Halothane induction in children results in significant reduction in heart rate and blood pressure. Bradyarrhthmias are uncommon with promethazine premedication.

Anesthesia, Inhalation↗
PubMed2006

Inhibition of rat brain ecto-atpase activity by various drugs.

The in vitro effect of digoxin, verapamil, propranolol, carbamazepine, diazepam and promethazine were investigated on the ecto-ATPase activity of synaptosomal plasma membranes from the rat brain. ATP hydrolyzing activities of the enzyme were not affected by digoxin while the use of all other drugs resulted in significant and dose-dependent ihibition in ATP hydrolysis. According to values of IC(50) and K(iapp), the order of inhibitory potency of the drugs applied was: diazepam > promethazine > verapamil > propranolol >> carbamazepine. Kinetic analysis of the nature of the ATPase inhibition revealed that it resulted from a direct action of drugs on the enzyme protein. The aim of the present study was to determine the potential neuromodulatory side effects of the drugs investigated. The results achieved indicated that all investigated drugs, except digoxin, may modulate neuronal activities via the purinergic receptors P2 by increasing extracellular concentrations of ATP as a consequence of inhibition of the ecto-ATPase activity. Our findings indicate that it may be useful to take into consideration the possible side effects of the investigated drugs, when they are used in treatment of different pathologies, particularly in the treatment of epilepsy by carbamazepine and diazepam.

Adenosine Diphosphate↗
PubMed1990

Sorption of various drugs in polyvinyl chloride, glass, and polyethylene-lined infusion containers.

The sorption of chloroquine sulfate, diazepam, isosorbide dinitrate, lorazepam, midazolam, nitroglycerin, promethazine hydrochloride, thiopental sodium, and warfarin sodium to three types of containers was studied. Appropriate amounts of the drugs were added to 500 mL of 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags, glass bottles, and Clear-Flex bags composed of a laminate of polyethylene, nylon, and polypropylene. The containers were stored in the dark at room temperature for 24 hours. Samples were taken at various intervals and assayed for drug concentration by high-performance liquid chromatography. There were no appreciable changes in pH after 24 hours, and all the admixtures remained clear and colorless. The potency of chloroquine sulfate, lorazepam, midazolam, promethazine hydrochloride, and thiopental sodium remained unchanged in glass, PVC, and Clear-Flex containers. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium did not show any sorption to glass bottles and Clear-Flex bags. In PVC bags, however, up to 55% of diazepam, 23% of isosorbide dinitrate, 51% of nitroglycerin, and 24% of warfarin sodium was lost during the 24-hour study period. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium in 0.9% sodium chloride injection showed a loss of potency when stored in PVC containers for 24 hours at room temperature, but none of the drugs studied lost potency when stored in glass bottles and Clear-Flex bags.

Adsorption↗
PubMed1978

A repeated dose comparison of the side effects of five antihistamines on objective assessments of psychomotor performance, central nervous system arousal and subjective appraisals of sleep and early morning behaviour.

The side effects of five antihistamines (chlorpheniramine maleate, mebhydrolin, clemastine hydrogen fumarate, Tavegil; ketotifen, and promethazine hydrochloride) were measured on subjective assessments of sleep and the integrity of early morning behaviour and objective assessments of complex psychomotor behaviour and central nervous system arousal. Fifty consenting volunteers each received one of the five preparations for a period of four days with the subjective effects being reported on a set of 10 cm line visual analogue scales and the objective assessments being made via a computer assisted reaction time task and critical flicker fusion thresholds. Chlorpheniramine, 4 mg t.d.s. for four days, produces a significant impairment in critical flicker fusion thresholds with respect to pretreatment baselines but none of the preparations showed any significant impairment in complex reaction time assessments. The subjective assessments of sleep and early morning hangover showed mebhydrolin and clemastine to be free from detrimental side effects, but promethazine and chlorpheniramine produce significant impairments in the integrity of early morning behaviour.

Adult↗
PubMedDate not supplied

Rapid microchemical identification of four phenothiazine antiemetics with gold bromide and iodine-potassium iodide reagents: collaborative study.

A microchemical method was developed for the rapid identification of 4 phenothiazine antiemetics. Perphenazine, promethazine, thiethylperazine, and triflupromazine were positively identified and differentiated with the aid of a gold bromide reagent and an iodine-potassium iodide reagent. Only promethazine and triflupromazine yielded microcrystalline derivatives with gold bromide; only perphenazine and thiethylperazine reacted with iodine-potassium iodide. For each pair of positive reactions, the crystalline products were morphologically distinguishable under a microscope. The 2 tests were collaboratively studied by 7 independent laboratories and found to be simple, rapid, and effective for identifying the phenothiazines of interest. The method has been adopted official first action.

Antiemetics↗
PubMed1979

Effect of antihistamines on anaphylactoid oedema in rats using a modified plethysmometer for measuring foot volume.

This study reports the quantitative effect of the H1--and H2--receptor antagonists on dextran-induced anaphylactoid oedema in rats. The findings indicate that mepyramine, promethazine and chlorpromazine which are H1--receptor antagonists significantly inhibited this anaphylactoid oedema. While on the other hand burimamide an H2--receptor antagonist at doses below 500 micrograms/kg inhibit dextran-induced oedema but at higher doses enhances oedema formation in the test rats. E.D50 values obtained for mepyramine, chlorpromazine and promethazine are 5.01 mg/kg, 0.36 mg/kg, 1.78 mg/kg respectively. The dual effects of burimamide on dextran-induced oedema merits further investigation and confirmation with the aid of other H1--and/or H2--receptor systems. A modification of the plethysmometric method of Buttle et. al. (1957) is also described.

Anaphylaxis↗
PubMed1981

[Pharmacological study of mequitazine (LM-209) (III). Action on the central nervous system (author's transl)].

The action of an anti-histaminic agent, Mequitazine (LM-209) on the central nervous system was investigated. We found that LM-209 did not affect the spontaneous and co-operative movement in mice, did not induce muscle relaxation, analgesic effects or anti-convulsant effect in micr or hypothermic effects in rats. The anti-oxotremorine effect of LM-209 in mice was about 10 times more potent than clemastine fumarate (CL) and the same as promethazine. The activity and duration of the action were also superior to diethazine and orphenadrine used as an anti-Parkinson drug. LM-209 prolonged by 50% the hypnotic time induced by hexobarbital at 50 mg/kg (p.o.) in mice, while CL prolonged 50 and 100% it at 25 and 50 mg/kg (p.o.) respectively. In the EEG of rabbits, LM-209 produced a resting pattern, inhibited the arousal responses and recruiting responses and the effect was the same as CL and less potent than promethazine. From these results, the activity of LM-209 on the central nervous system (except for the anti-oxotremorine effect) seems to be the same as or somewhat less potent than CL. Therefore LM-209 should be an effective and anti-histaminic agent for clinical application.

Analgesics↗
PubMed1981

The effect of the antihistaminic drugs on the central action of 5-hydroxytryptophan in mice.

Antihistaminic drugs of various chemical structure (chlorcyclizine, chloropyramine, chlorpheniramine, clemastine, diphenhydramine, mepyramine, promethazine, thenalidine) were tested on their action on the central serotonin system in mice. The test used was the antagonism to behavioral syndrome produced by D, L-5-hydroxytryptophan (5-HTP). Clemastine, promethazine and thenalidine inhibited 5-HTP-induced syndrome in doses of much lower than those inhibiting locomotor activity. Similar but weaker effect was produced by chlorcyclizine and diphenhydramine. It could be suggested that these compounds exert central antiserotonergic action. Chloropyramine and, more strongly, chlorpheniramine potentiated the action of 5-HTP; this may be due to the inhibition of serotonin uptake. Only mepyramine in these tests did not show any action on the central serotonin system.

5-Hydroxytryptophan↗
PubMedDate not supplied

[The importance of histaminergic H1 and H2 receptors for the contractile effect of histamine on human umbilical veins].

Influence of histamine and histaminergic H1 blockers (antazoline, promethazine) and H2 blockers (cimetidine, ranitidine) on isometric contraction of helically cut strips of human umbilical vein was examined. Histamine produced dose-related contraction of the vein strip, while histaminergic H1 and H2 blockers did not changed the tonus of the vein. The contractile activity of histamine was not influenced by cimetidine or ranitidine, while antazoline and promethazine antagonized mentioned activity of histamine completely. We suppose that histamine exerts contractile effect of human umbilical vein by acting on H1 receptors while H2 receptors are not involved in the mentioned activity of histamine.

Histamine↗
PubMedDate not supplied

[Effect of histamine and its antagonists on the muscular tone of the non-pregnant uterus in the woman].

In the isolated strips of the individual parts of the human uterus (body, corns, cervix) histamine, promethazine, and cimethidine, proportionally to the dose applied, have proved to increase the muscular tonus. The blocking agents of histamine H-1 receptors (promethazine) and H-2 receptors (cimetidine), separately or jointly administered in the dose of 10 micrograms/ml, significantly diminish the tonicizing effect of histamine. The effect of histamine on the uterine muscular tonus is brought about through histamine H-1 and histamine H-2 receptors.

Female↗
PubMedDate not supplied

[Effect of histamine and its antagonists on the muscle tone of the body of the non-pregnant and pregnant human uterus].

In the uterus body of nongravid and gravid women, proportionally to the dose used, histamine, promethazine, and cimetidine produce an increased muscular tonus, which is more pronounced in gravid uteri. The blocking agent of histamine H-1 receptors, promethazine, and the blocking agent of histamine H-2 receptors, cimetidine, separately or jointly applied in a dose of 10 micrograms/ml, significantly decrease the tonicizing effect of histamine. Histamine exerts its influence on the muscular tonus of the body of nongravid and gravid human uteri through histamine H-1 and histamine H-2 receptors.

Female↗
PubMed1983

Application of a primate model for tardive dyskinesia.

Persistent signs of oral dyskinesia (tongue protrusion and facial grimacing) had developed as a result of earlier chronic treatment with neuroleptics in a Cebus apella monkey. When this animal was given single doses of any classical neuroleptic, a transient deterioration of dyskinesia occurred, preceded by a temporary abolishment of dyskinesia sometimes with an attack of acute dystonia. Fluphenazine (5-25 micrograms/kg) causes dose-related deteriorations of dyskinesia. Six different drugs were tested on this monkey for their capacity to elicit aggravation of dyskinetic signs: three antihistamines (brompheniramine, promethazine, diphenhydramine) and three dopamine D2 receptor antagonists (sulpiride, tiapride, metoclopramide). High doses of promethazine and diphenhydramine (5 mg/kg) induced a temporary alleviation of dyskinesia, possibly through sedation. All three D2 receptor antagonists precipitated signs of acute dystonia at some dose levels, but out of the test drugs only metoclopramide caused deterioration of dyskinetic symptoms. According to the present results only metoclopramide stands out as a drug with an inherent propensity to cause tardive dyskinesia.

Animals↗
PubMed1978

[Fluorescence-analytical studies of the reaction of several psychoactive drugs with membrane structures of the CNS].

The use of 1-anilino-8-naphthalene sulfonate (ANS) as an indicator of membrane conformational perturbations induced by psychoactive drugs was tested with regard to its specificity considering both chemical structure (phenothiazine, butyrophenone, phenylalkylhydrazine) and pharmacological activity (major transquilizers, antidepressants, antihistamines), on the one hand, and brain region (cortex, striatum, hippocampus) and subcellular structure of membranes (mitochondria, microsomes, synaptosomes), on the other. Not only a weak strengthening of ANS affinity to membrane constituents by chlorpromazine and promethazine (haloperidol and phenelzine were without effect), but also the alteration of membrane structure in such a way as to create additional ANS binding sites by chlorpromazine and to a smaller degree also by promethazine and haloperidol (phenelzine was without effect) resulting in a manifold increase in fluorescence indicated any relation to functional characteristics of biological material or properties of drugs. Apparent dissociation constants and membrane ANS binding sizes are reported.

Anilino Naphthalenesulfonates↗