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PubMed1976

Recent developments in the drug treatment of schizophrenia.

The author reviews six topics relevant to the drug treatment of schizophrenia. The quantitative effectiveness of promazine is of interest with respect to the structural models of the phenothiazines and the dopamine theory of schizophrenia. The quantitative effectiveness of antipsychotic drugs is also important in evaluating new agents and therefore relevant to a discussion of two newly released neuroleptics, molindone and loxapine. The author's discussion of high-dose treatment of typical acute schizophrenics or treatment-resistant patients reviews the available data and calls attention to the fact that these areas of pharmacologic research have not received sufficient attention.

Chlorpromazine↗
PubMed2001

Spectrophotometric determination of vanadium(V) in minerals, steels, soil and biological samples using phenothiazine derivatives.

Two simple, rapid and sensitive spectrophotometric methods have been proposed for the determination of vanadium(V) using butaperazine dimaleate (BPD) and propionyl promazine phosphate (PPP). These methods are based on the formation of red-colored radical cations on reaction with vanadium(V) in phosphoric acid medium, with their absorbance maxima at 513 nm. Beer's law is valid over the concentration range of 0.25-5.0 micrograms ml-1 and 0.2-4.0 micrograms ml-1, with Sandell's sensitivity values of 6.1 ng cm-2 and 6.0 ng cm-2 for BPD and PPP respectively. The proposed methods have been successfully applied to the analysis of vanadium steels, minerals, biological samples and soil samples.

Humans↗
PubMed2000

Effects of general anesthesia and surgery on renal function in healthy dogs.

OBJECTIVES: To evaluate renal function in healthy dogs undergoing general anesthesia and ovariohysterectomy without concurrent IV administration of fluids. ANIMALS: 35 healthy client-owned dogs. PROCEDURE: Dogs were medicated with promazine hydrochloride (0.05 mg/kg of body weight, SC) approximately 45 minutes before induction of anesthesia with thiopental sodium (10 to 15 mg/kg, IV). Anesthesia was maintained with 2% halothane in oxygen. Ovariohysterectomies were performed by senior veterinary students under the direct supervision of a veterinary surgeon. Renal function was assessed (serum urea and creatinine concentrations, fractional clearance of sodium, urine alkaline phosphatase [ALP] and gamma-glutamyltransferase [GGT] activities, urine specific gravity, and enumeration of renal tubular epithelial cells in urine sediment) prior to and 24 and 48 hours after surgery. RESULTS: Duration of general anesthesia ranged from 80 to 310 minutes. Urine specific gravity and ALP activity and serum urea and creatinine concentrations did not change over time. Fractional clearance of sodium decreased 24 and 48 hours after surgery, whereas urine GGT activity and the ratio of urine GGT activity to urine creatinine concentration increased 24 hours after surgery, compared with presurgery values. Renal tubular epithelial cells increased in number in urine sediment from 11 of 35 (31.4%) dogs and 5 of 35 (14.3%) dogs 24 and 48 hours after surgery, respectively. However, this increase was not clinically relevant. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of fluids to healthy dogs undergoing general anesthesia and elective surgery may not be necessary for maintenance of renal homeostasis.

Alkaline Phosphatase↗
PubMed1982

Comparison and assessment of drugs used to immobilize Alaskan gray wolves (Canis lupus) and wolverines (Gulo gulo) from a helicopter.

One hundred and three Alaskan gray wolves and 12 wolverines were immobilized in the Nelchina and upper Susitna River Basins of southcentral Alaska between March 1977 and May 1981. Sixty-five wolves were immobilized with a mixture of phencyclidine HCl and promazine HCl (PP/HCl); 38 wolves were immobilized with etorphine HCl (EHCl) and 12 wolverines were immobilized with EHCl or with a mixture of EHCl and xylazine HCl (XHCl). Phencyclidine HCl is no longer commercially available and an assessment of etorphine HCl as a replacement drug was made. Etorphine HCl dosage of 2.5 mg/wolf proved to be a suitable replacement for PP/HCl for immobilizing wolves while 0.7 mg EHCl with 50 mg XHCl appeared suitable for wolverines.

Aircraft↗
PubMed1976

[Psychotropic drugs for behavior disorder treatment in oligophrenic epileptics].

Forty-one patients were treated with promazine, a phenothiazine derivative, for an average of 266 days. The average daily dose was 200 mg. Thirty patients were treated with levomepromazine for an average of 115 days, the daily dose being about 130 mg. The two groups of patients were examined for their contactual, impulsive, and affective behavior before, during, and after treatment. The positive results obtained justify the use of the above-mentioned psychopharmaceuticals for the therapy of abnormal behavior of oligophrenic epileptics.

Adult↗
PubMed1976

[Combined anesthesia with propionylpromazine (Combelen) and methadone (Polamivet). A sure simple method of anesthesia in gastrointestinal surgery in dogs].

In more than 400 cases of gastrointestinal surgery on mongrel dogs, a combination anesthesia of a neuroplegic agent--propionyl promazine (Combelen) and methadone (Polamivet), an analgesic--was administered without additional intubation or ventilation. This type of anesthesia is simple to apply and practically without risk; the conditions for the operation are therefore excellent. No monitoring personnel is required, no intra- or post-operative incidents have occurred. Thus this method may be recommended as safe and simple for experimental abdominal surgery in dogs.

Anesthesia, Intravenous↗
PubMed1975

The role of discriminative stimuli in modulating drug action.

Behavior reinforced in the presence of a stimulus comes under the control of the stimulus. A drug can then modify that control and, therefore, modify the behavior itself. Studies over the past 2 decades have shown that the nature of the controlling (or discriminative) stimulus can govern the degree to which drugs change performance. These experiments usually have compared behavior on various schedules of reinforcement with and without added discriminative stimuli. For instance, pigeons that had been trained on a fixed-interval schedule showed great changes in response distribution after amphetamine and scopolamine. The same birds, when performing on a fixed-interval schedule to which time-correlated discriminative stimuli had been added, showed smaller changes in response distribution. Other pigeons were trained to make a minimum number of consecutive responses on one key before a peck on a second key would be reinforced; beta-amphetamine and scopolamine led to pronounced increases in premature switching. Adding a discriminative stimulus when the response requirement was fulfilled increased the likelihood that a switch would occur only after the appropriate number of pecks had been emitted. It also attenuated the effects of the drugs. The presence of discriminative stimuli did not make as large a difference in performance in either of these experiments when chlorpromazine and promazine were studied. In general, work with other schedules of reinforcement supports the conclusion that behavior under stron external stimulus control is less apt to be readily affected by many drugs. Addition of the discriminative stimulus can also "improve" the behavior of pigeons that have been given enough methylmercury to increase greatly the variability of their performance.

Amphetamine↗
PubMedDate not supplied

Densitometric high performance thin-layer chromatography identification and quantitative analysis of psychotropic drugs.

A thin-layer chromatography (TLC)-densitometry method has been developed to identify and quantify haloperidol, amitriptyline, sulpiride, promazine, fluphenazine, doxepin, diazepam, trifluoperazine, clonazepam, and chlorpromazine in selected psychotropic drugs. Separation was performed on precoated silica gel 60 F254 TLC plates. Chromatograms were developed in various mobile phases, and 8 of 30 tested phases were selected based on spot location and developing time. The identification and quantification were carried out based on ultraviolet densitometric measurements at chosen wavelengths. In addition to retention coefficients, the absorption spectra recorded directly from chromatograms were also used in qualitative analysis. Under established experimental conditions, high sensitivity of the method was achieved. The limit of detection ranged from 0.009 to 0.260 microg, depending on the wavelength selected for measuring. A satisfactory recovery, ranging from 92.99 to 104.70%, was achieved for individual constituents.

Amitriptyline↗
PubMed1991

[Study on the multiwavelength coefficient spectrophotometry and its application].

This paper reveals a general principle of multiwave length spectrophotometry and puts forward a multiwave length coefficient method to determine mixed components system. The determination of the coefficients and the connection between the coefficients with the method are discussed in the paper. Using several groups of coefficients, according to the method, a mixed components of chlorpromazine hydrochloride and promazine hydrochloride were assayed at the same time. The laboratory results of recoveries indicates that the precision and the accuracy are good, and, different coefficients do not make a notable impact on the method.

Chlorpromazine↗
PubMed1990

[Comparative clinical studies of oral premedication in childhood with reference to various pharmaceuticals].

In a randomized prospective study of 206 children aged between one and 14, the influence of oral praemedication on the psychic condition and with regard to anaesthesiologic measures was investigated. Heart rate, inhibition of salivation and the kind and frequency of side-effects were also examined. The praemedication was carried out using diazepam (0.3 mg/kg), promazin (1.0 mg/kg), promethazin (1.0 mg/kg) and chlorphenaethazin (1.0 mg/kg). It was not possible to determine statistically relevant differences between the various drugs concerning the fixed criteria. In general, however, diazepam seems to achieve the best results. In the younger children (1 to 6 years) a frequent and insufficient effect of praemedication was noted immediately. Oral praemedication proved to be a valuable and practicable method which was well tolerated by the great majority of the children.

Administration, Oral↗
PubMed1979

Phenothiazine analgesia--fact or fantasy?

Double-blind clinical trials involving the use of phenothiazines as analgesics or potentiators of analgesics (aspirin, meperidine, morphine sulfate) and adverse effects of phenothiazines are reviewed and evaluated. Promethazine, promazine and propiomazine were not found to possess analgesic or potentiating properties. One chlorpromazine study contained important design and reporting deficiencies which precluded a recommendation for use of chlorpromazine in the treatment of pain. Methotrimeprazine was determined by numerous authors to have analgesic properties; however, most of the studies also were deficient in design or data presented, or both. Adverse reactions to phenothiazines, including hypotension, sedation, drowsiness, extrapyramidal symptoms, tardive dyskinesia, cardiac toxicity and agranulocytosis, are often more common and severe than those attributed to narcotic analgesics. Because of the lack of data supportive of analgesic activity and the adverse reactions associated with phenothiazines, use of these agents in the management of pain should be discouraged. The prophylactic use of phenothiazine for narcotic analgesic-induced emesis also is, in most cases, a questionable practice.

Analgesics↗
PubMed1986

A theoretical study of the binding of phenothiazine derivatives to residues 82-93 of calmodulin.

A theoretical study was performed of the interaction of four phenothiazine derivatives, promethazine, promazine, trifluopromazine, and trifluoperazine, with a fragment (82-93) of calmodulin, held in the alpha-helical conformation. The computations were performed in the framework of the SIBFA 2 procedure (sum of interactions between fragments computed ab initio), which uses analytical formulas based on ab initio self-consistent field computations. The interaction energy is the sum of the intermolecular phenothiazine-oligopeptide interaction energy and of the separate intramolecular energy variations of the phenothiazine and of the side chains of the oligopeptide upon complex formation. The ordering of interaction energies of the four investigated phenothiazines parallels the ordering of their experimentally measured affinities for calmodulin, with a maximum affinity for trifluoperazine. The principal features of the trifluoperazine complex are a short hydrogen bond between the piperazinium proton and one anionic oxygen of Glu 87, and hydrophobic interactions between the piperazinium ring and Val 91 and between the methylene chain and Ala 88, together with partial insertion of the phenothiazine ring and the--CF3 substituent between Phe 89 and Phe 92.

Calmodulin↗
PubMed1983

[In vitro studies on the adsorption of various resins of the Wofatit type for drugs].

The capacities of the resins Wofatit Y 29, Y 55 and Y 56 (VEB Chemiekombinat Bitterfeld) to adsorb various medicaments were compared with that of the resin XAD-4. Methaquelone, diazepam, krotylbarbital, promazine phosphate and ethyloxamine were used as test substances. The resin Y 56 proved to have an adsorption capacity similar to that of XAD-4 (e.g. maximum saturation for methaquelone 98%, half-maximum saturation at 7 minutes). In further tests on various batches of this resin the best results were given by the resin Y 56/7. Adsorption was quite clearly shown to be dependent on concentration. At a blood-flow of 100 ml/min clearance values of 34.5 ml/min for krotylbarbitol and 22.1 ml/min for methaquelone were calculated. According to these findings the resin Y 56/7 is suitable for further testing in a haemoperfusion system with a view to clinical use.

Barbiturates↗
PubMed1984

Analysis of propionylpromazine and its metabolites in horse urine.

The metabolism of propionylpromazine in the horse was studied. Although propionylpromazine is not currently approved or recommended for use in horses, it has been used illegally to alter their performance. Propionylpromazine hydrochloride was administered intramuscularly at clinical and subclinical doses. Three metabolites were detected in urine. The major metabolite was identified as 2-(1-hydroxypropyl) promazine sulfoxide. The detection of this metabolite in routine drug testing has been described.

Animals↗
PubMedDate not supplied

Inhibition of Escherichia coli haemagglutination by phenothiazines.

The enterotoxigenic Escherichia coli strain H-10407 (078-H11) of Evans, possessing a colonization factor antigen (CFA/I) and haemagglutinating in the presence of mannose, was tested as to its ability to cause haemagglutination in the presence of phenothiazines. The phenothiazines (chlorpromazine, thioridazine, prochlorperazine, triethylpiperazine, promethiazine and promazine) were able to inhibit E. coli haemagglutination when added to the complex E. coli-erythrocytes. The most potent inhibitors were prochlorperazine and thioridazine, which inhibited E. coli haemagglutination in 1 min at a concentration of 1.5 mg/ml. The less potent was promethazine that inhibited haemagglutination at 6 mg/ml. Once haemagglutination had occurred the phenothiazines were able to reverse it, to "unhood" the E. coli from the erythrocytes. Prochlorperazine at a concentration of 0.4 mg/ml could reverse haemagglutination after 1 h contact with the E. coli erythrocytes complex. E. coli H-10407 grown in the presence of phenothiazines lost its haemagglutinating activity. The resulting non haemagglutinating E. coli recovered its haemagglutinating activity when recultured in a prochlorperazine free medium.

Chlorpromazine↗
PubMed2003

Direct injection HPLC method for the determination of selected phenothiazines in plasma using a Hisep column.

A direct plasma injection HPLC method has been developed for the determination of selected phenothiazines (promethazine, promazine, chlorpromazine) using a Hisep column. The method is easy to perform and requires 20 microL of a filtered plasma sample. The chromatographic run time is less than 11 min using a mobile phase of 15:85 v/v acetonitrile-0.18 m ammonium acetate pH 5.0 and UV detection at 254 nm. The method is linear in the concentration range 0.1-25 microg mL(-1) (r > 0.99, n = 6) for each analyte with RSD less than 6%. Interday and intraday variability were found to be < or =14%. The limits of detection and quantitation were 0.1 (S/N > 3) and 0.25 microg mL(-1) (S/N > 10), respectively, for each of the three phenothiazines. We can also apply this method to separate three other phenothiazines (ethopromazine, trifluoroperazine, prochlorperazine), although it lacks the selectivity to determine the concentration of all six drugs concurrently. The separation is feasible using these drugs in certain combinations.

Chromatography, High Pressure Liquid↗
PubMed2004

Halogenation of drugs enhances membrane binding and permeation.

Halogenation of drugs is commonly used to enhance membrane binding and permeation. We quantify the effect of replacing a hydrogen residue by a chlorine or a trifluoromethyl residue in position C-2 of promazine, perazine, and perphenazine analogues. Moreover, we investigate the influence of the position (C-6 and C-7) of residue CF(3) in benzopyranols. The twelve drugs are characterized by surface activity measurements, which yield the cross-sectional area, the air-water partition coefficient, and the critical micelle concentration. By using the first two parameters (A(D) and K(aw)) and the appropriate membrane packing density, the lipid-water partition coefficients, are calculated in excellent agreement with the lipid-water partition coefficients measured by means of isothermal titration calorimetry for small unilamellar vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. Replacement of a hydrogen residue by a chlorine and a trifluoromethyl residue enhances the free energy of partitioning into the lipid membrane, on average by deltaG(lw) approximately -1.3 or -4.5 kJ mol(-1), respectively, and the permeability coefficient by a factor of approximately 2 or approximately 9, respectively. Despite exhibiting practically identical hydrophobicities, the two benzopyranol analogues differ in their permeability coefficients by almost an order of magnitude; this is due to their different cross-sectional areas at the air-water and lipid-water interfaces.

Benzopyrans↗
PubMed2005

Development and validation of a capillary electrophoresis method for the determination of phenothiazines in human urine in the low nanogram per milliliter concentration range using field-amplified sample injection.

A capillary zone electrophoresis (CZE) method with ultraviolet-visible detection has been established and validated for the determination of five phenothiazines: thiazinamium methylsulfate, promazine hydrochloride, chlorpromazine hydrochloride, thioridazine hydrochloride, and promethazine hydrochloride in human urine. Optimum separation was obtained on a 64.5 cm x 75 microm bubble cell capillary using a buffer containing 150 mM tris(hydroxymethyl)aminomethane and 25% acetonitrile at pH 8.2, with temperature and voltage of 25 degrees C and 20 kV, respectively. Naphazoline hydrochloride was used as an internal standard. Field-amplified sample injection (FASI) has been applied to improve the sensitivity of the detection. Considering the influence of parameters affecting the on-line preconcentration (nature of preinjection plug, sample solvent composition, injection times, and injection voltage) and due to the significant interactions among them, in this paper we propose for the first time the application of a multivariate approach to carry out the study. The optimized conditions were as follows: preinjection plug of water for 7 s at 50 mbar, electrokinetic injection for 40 s at 6.2 kV, and 32 microm of H3PO4 in the sample solvent. Also, a solid-phase extraction (SPE) procedure is developed to obtain low detection limits and an adequate selectivity for urine samples. The combination of SPE and FASI-CZE-UV allows adequate linearities and recoveries, low detection limits (from 2 to 5 ng/mL), and satisfactory precisions (3.0-7.2% for an intermediate RSD %).

Chemical Fractionation↗