Chlorpromazine HCl Research Articles

Development of Turbidimetric Methods for the Determination of Some N-Substituted Phenothiazine Derivatives Using Sodium Dodecyl Sulfate and Mercury(II) Chloride

Two turbidimetric procedures were developed for the determination of Fluphenazine·HCl (FPH), Chlorpromazine·HCl (CPH), Thioridazine·HCl (TH), and Trifluophenazine·2HCl (TFPH) in several pharmaceutical preparations using sodium dodecyl sulfate (SDS) (method A) and HgCl2 (method B) as precipitant reagents. Method A is based on the sparingly soluble ion-association complex formation between protonated phenothiazines and SDS. In method B, HgCl2 is reduced to insoluble Hg2Cl2 in the presence of phenothiazine derivatives. The Beer's law in method A was obeyed over the range 30–71.5, 14–106, and 8–57 µg mL−1 for CPH, FPH, and TH, respectively. TFPH, CPH, and TH were determined using method B over the range 14.4–191.7, 17.7–106.6, and 1–8.1 µg mL−1, respectively. The proposed methods are simple, fast, precise, economical, and applicable for the determination of selected phenothiazine drugs in formulations at a wide concentration range without any considerable interference.

Spectrophotometric Determination of Chromium in Ores, Steels and Pure Nickel Samples using Phenothiazines

Abstract A new, simple, and sensitive method has been developed for the spectrophotometric determination of CrVI based on its reaction with chlorpromazine-HCl (CPH) to give a red product. Under the optimum conditions, the linear range of the calibration graph was 0.00–0.33 µg mL−1 of CrVI. The molar absorptivity and the detection limit were 3.28 × 104 dm3 mol−1 cm−1 and 0.003 µg mL−1 of CrVI, respectively. Analyses of certified ores, steels, and pure nickel samples gave results in excellent agreement with the nominal values and with relative standard deviations of ≤ 1.5%

Ion-Pair Formation in Pharmaceutical Analysis. Conductimetric Determination of Promazine, Chlorpromazine, Promethazine, Imipramine and Ciprofloxacin Hydrochlorides in Pure Form, Drug Formulations and Urine

Potassium ferricyanide and sodium tetraphenylborate were used as titrants for the conductimetric determination of promazine HCl, chlorpromazine HCl, promethazine HCl, imipramine HCl and ciprofloxacin HCl through ion-associate complex formation. The molar combining ratio, effects of dilution of titrant, temperature and solvent were studied. The accuracy of the method is indicated by excellent recovery (99.50–99.96%). The sensitivity of the proposed method is discussed and the results are compared with the pharmacopoeial or the official methods. The suggested method has been applied for the analysis of the mentioned compounds in their pharmaceutical formulations and urine.

Chlorpromazine interaction with glycerophospholipid liposomes studied by magic angle spinning solid state 13C-NMR and differential scanning calorimetry

Phosphatidylserine (PS) extracted from pig brain and synthetic dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) were used to make DPPC/DMPC and DPPC/PS large unilamellar liposomes with a diameter of ∼1 μm. Chlorpromazine-HCl (CPZ), an amphipathic cationic psychotropic drug of the phenothiazine group, is known to partition into lipid bilayer membranes of liposomes with partition coefficients depending on the acyl chain length and to alter the bilayer structure in a manner depending on the phospholipid headgroups. The effects of adding CPZ to these membranes were studied by differential scanning calorimetry and proton cross polarization solid state magic angle spinning 13C-nuclear magnetic resonance spectroscopy (CP-MAS- 13C-NMR). CP-MAS- 13C-NMR spectra of the DPPC (60%)/DMPC (40%) and the DPPC (54%)/DMPC (36%)/CPZ (10%) liposomes, show that CPZ has low or no interaction with the phospholipids of this neutral and densely packed bilayer. Conversely, the DPPC (54%)/PS (36%)/CPZ (10%) bilayer at 25°C demonstrates interaction of CPZ with the phospholipid headgroups (PS). This CPZ interaction causes about 30% of the acyl chains to enter the gauche conformation with low or no CPZ interdigitation among the acyl chains at this temperature (25°C). The DPPC (54%)/PS (36%)/CPZ (10%) bilayer at a sample temperature of 37°C ( T C=31.2°C), shows CPZ interdigitation among the phospholipids as deduced from the finding that ∼30% of the phospholipid acyl chains carbon resonances shift low-field by 5–15 ppm.

Preparation and Characterization of Hyaluronate-Hydroxyethyl Acrylate Blend Hydrogel for Controlled Release Device.

Hyaluronate-hydroxyethyl acrylate blend hydrogels were investigated as matrices for controlled release devices. Glycidyl methacrylate (GMA) derivatized HA (GMA-HA) was synthesized by coupling of GMA to HA in the presence of a suitable catalyst. These hydrogels were prepared by a free radical copolymerization of GMA-HA and hydroxyethyl acrylate. The water content of these hydrogels at equilibrium swelling in water (Ww) was 0.978+/-0.0073 (n=18); however, these hydrogel was mechanically tough and could be used as disk shape. The hydrogels swelling were found to depend on ionic strength and pH. The dried hydrogels quickly regained their original condition in water, and they swelled to more than 90% of its initial water contents after 30 min. This swelling-deswelling behavior was reproducible. The release of chlorpromazine HCl as a model cationic drug from the gels was suppressed significantly in water. The release increased with increasing the ionic strength and decreasing pH of bulk solutions.

Application of Ion-Pairs in Pharmaceutical Analysis. Atomic Absorption Spectrometric Determination of Promazine, Chlorpromazine, Promethazine, Imipramine and Ciprofloxacin Hydrochlorides with Sodium Cobaltinitrite

ABSTRACT Ion-association complexes of promazine HCl (I), chlorpromazine HCl (II), promethazine HCl (III), imipramine HCl (IV) and ciprofloxacin HCl (V) with [Co(NO2)6]3− were precipitated at their optimum conditions of pH and ionic strength (NaCl-HCl/NaOH) and the excess unreacted cobalt complex was determined using atomic absorption spectrometry (AAS). The applicability of the method for determination of the above drugs in pure solution, pharmaceutical preparations and urine was examined. The drugs can be determined in the ranges 0.485-4.854, 1.619-16.197, 1.441-14.410, 1.415-14.154 and 0.578-5.787 mg/25 ml of I, II, III, IV and V, respectively, with mean relative standard deviations 1.05-1.53% and recovery values of 98.85±0.31-100.09±0.54% indicating high precision and accuracy. The sensitivities of the proposed method were 11.73, 23.00, 30.00, 38.00 and 12.69 μg/ml for the drugs I, II, III, IV and V, respectively; and the detection limits for determination of the investigated drugs were 3.10, 7.20, 13.80, 18.30 and 6.63 μg/ml for I, II, III, IV and V, respectively. The suggested method has been applied for the determination of the above mentioned drugs in their pharmaceutical formulations and urine.

Spectrofluorimetric Determination of Chlorpromazine Hydrochloride and Thioridazine Hydrochloride

Abstract Fluorescence spectroscopy was applied to the development of a sensitive and simple method for the determination of chlorpromazine HCl and thioridazine-HCl. The method is based upon development of an intense fluorescence using N-bromosuccinimide as the fluorogenic reagent. The produced fluorescence has very characteristic excitation and emission spectra and was stable for at least one hour. The results were reproducible and as little as 5 ng/ml chloropromazine HCl and 1 ng/ml thioridazine-HCl could be determined. The method was applied successfully to the analysis of various commercially available dosage forms. The obtained results were in good agreement with those of the official BP 93 procedures.

Effect of interpolymer complex formation of chitosan with pectin or acacia on the release behaviour of chlorpromazine HCl

The interpolymer complexes of chitosan with pectin and acacia were investigated using viscosity measurements. The binding ratios of the complexes were found to be 1:10 and 1:20 for chitosan-pectin and chitosan-acacia, respectively. The solid complexes were separated and dried to be used as tablet matrices. The release of the water-soluble chlorpromazine HCl from tablets containing various concentrations of each of the polymers alone, the complexes or physical mixtures of chitosan and of pectin and acacia in the same ratio of their respective complexes, was evaluated. Increasing the concentrations of the polymers, complexes or the physical mixtures in the tablets retarded drug release. The effect of different polymers on drug release was dependent on the gel property of the polymers and the drug-polymer interaction. The physical mixture displayed the most efficient sustained release. The results were explained.

Estudo da associação clorpromazina + quetamina em cães

Com o objetivo de avaliar a possibilidade de associação e aplicação do cloridrato de quetamina e cloridrato de clorpromazina, por via intramuscular em cães, foi idealizado o presente experimento. Foram utilizados 10 animais adultos, de ambos os sexos, sem raça definida, com peso médio de 17 kg. A cada cão foi administrado 1 mg/kg de peso corpóreo de clorpromazina associado, numa mesma seringa, a 15 mg/kg de quetamina e aplicado por via intramuscular profunda. Foram avaliadas as freqüências cárdio-respiratórias, temperatura retal, valores/hemogasométricos, glicemia e traçados eletrocardiográficos, sendo os valores numéricos tratados pelo teste de Tuckey a 5% de probabilidade. Constatou-se aumento significativo da freqüência cardíaca, além de constantes supra e infradesnivelamento do segmento ST quando da análise eletrocardiográfica, sendo os demais valores de pouca relevância estatística. Concluiu-se que a associação pode ser empregada em pacientes hígidos, mas pressupõem-se cuidados quando do uso em cães portadores de cardiopatias.

Spectrophotometeric determination of someN-substituted phenothiazine derivatives usingN-bromophthalimide

A simple, rapid and sensitive spectrophotometric method is described for the quantitative determination ofN-substituted phenothiazines. The method depends on the formation of a stable phenothiazine free radical cation by the use ofN-bromophthalimide as oxidising agent in a strong acid medium (methanol/ sulphuric acid 1∶ 1 v/v). The produced red or violet color possesses absorption maximum range from 500 to 530 nm. A linear relationship exists between the absorbance at (λmax) and concentration in the range 5 to 40 μg ml−1 with apparent molar absorptivities range from 6 × 103 to 12 × 1031 mol−1 cm−1. The color is developed instantaneously for all the studied phenothiazines except for thioproperazine mesylate, trifluoperazine dihydrochloride and prochlorperazine mesylate that require 25, 15 and 25 min, respectively, for complete reaction. The developed colors are stable over 24 h. The average % recovery is 99.85±0.61 to 100.28±0.95. The method was applied successfully to the microdetermination of chlorpromazine HCl, promethazine HCl, pericyazine, thioproperazine mesylate, perphenazine, prochlorperazine mesylate, trimeprazine tartrate and trifluoperazine 2HCl either in pure form or incorporated in their pharmaceutical preparations. The results of analysis are in good agreement with those of the official B.P. 1988 and USP XXII.

Compatibility problems of chlorpromazine HCl-stearate lubricants examined by differential scanning calorimetry

Differential scanning calorimetry (DSC) was used to investigate the interactions between chlorpromazine HCl (CPZ) and stearate lubricants. The phase diagram was constructed for each CPZ-stearate system. An unknown endothermic peak at 145°C was found for the CPZ-stearate lubricants; this was affected by the grinding and heating processes. This unknown endothermic peak proved to relate to a polymorphism transition but was not an incompatibility problem. Three polymorphisms of CPZ were also determined by DSC analysis and IR spectrophotometry.

PH-dependent phase transition of chlorpromazine micellar solutions in the physiological range

The effects of pH and drug concentration on aggregation properties of chlorpromazine-HCl (CPZ) are examined. The critical micelle concentration (cmc) changes from 0.2 mM at pH 7.3 to 2 mM at pH 5.6 as estimated from the stearic acid spin label solubility measurements. For concentrations above the cmc CPZ micelles undergo a concentration-, temperature- and pH-dependent transition leading to phase separation. This phase transition is followed by a sudden increase of light scattering. The phase diagram pH vs. concentration is obtained by observation of the cloud point for concentrations ranging from 0.01 to 10 mM. The intramicellar environment is probed at pH ranging from 5.5 to 8.0 using a stearic acid spin label. The intramicellar compactness increases smoothly with increasing pH suggesting the weakening of polar heads repulsion due to charge decrease. The reported results indicate that pH effects are relevant and should be properly taken into account in the performance and interpretation of experiments with CPZ.

Validation of a photobeam system for assessment of motor activity in rats

To evaluate the validity and sensitivity of test procedures for routine assessment of chemically induced changes in motor activity in rats, studies were carried out with a commercially available photocell cage system. Testing of single, untreated rats showed that motor activity decreased within 10 min to a steady level. Overall activity was the same when testing was repeated at weekly intervals for 6 weeks. In groups of each 10 rats tested immediately after i.p. injection, chlorpromazine HCl (6 or 2 mg/kg) and physostigmine salicylate (0.5 mg/kg) decreased activity. d-Amphetamine sulfate (1.0 mg/kg) caused an increase of virtually all parameters, whereas scopolamine HCl (1.0 mg/kg) and physostigmine salicylate (0.02 mg/kg) led to an increase of particular aspects of motor activity only. Data generated with a mechanical calibrator varies 1–5% between the cages tested. It is concluded that the above procedures of recording of selected parameters of motor activity in groups of 10 rats for periods of up to 20 min would comply with the guidelines recommended by EPA TOSCA [1].

Methodological proposal in behavioural teratogenicity testing: assessment of propoxyphene, chlorpromazine, and vitamin A as positive controls.

Pregnant Sprague-Dawley rats received either 80 mg/kg d-propoxyphene HCl or 20 mg/kg chlorpromazine HCl or 80,000 and 160,000 IU/kg vitamin A palmitate daily between the 6th and 20th days of gestation. Vehicle control groups were similarly treated with saline or corn oil and considered as negative controls. Offspring were examined for physical landmarks, neuromotor development, and behaviour using righting reflex, swimming, negative geotaxis, open field, rotarod, water maze, and nocturnal activity. This test battery included biochemical measurements. No reduction in parental weight and physical offspring development was observed. All these treatments produced long-term changes in more than one test. Vitamin A palmitate (160,000 IU/kg) was judged as the best positive control with this test battery for future investigation of the behavioural teratology of drugs.

Electrochemical analysis of some phenothiazine derivatives — I. Chlorpromazine HCl

In this study the electrochemical behaviour of chlorpromazine hydrochloride in sulphuric acid solutions has been examined by cyclic and linear sweep voltammetry using oxidised and non-oxidised ruthenium wire electrodes. Although a stable and permanent RuO 2 coating on the electrode took a long time to prepare, the resulting curves were highly reproducible. It was possible to study solutions in a wide concentration range only by use of scan rates lower than 20 mVs −1. The cyclic voltammograms of chlorpromazine hydrochloride in solutions of different concentrations of sulphuric acid and the behaviour of oxidised and non-oxidised ruthenium electrodes have been compared.

Evaluation of oral skeletal muscle relaxants in the morphine‐induced straub tail test in mice

AbstractMorphine is known to produce a characteristic and reproducible elevation of the tail in mice (Straub tail response). The morphine‐induced Straub tail response in mice has been used to evaluate skeletal muscle relaxant (SMR) activity of compounds administered intraperitoneally (i.p.). This model was used to evaluate the oral (p.o.) efficacy of a number of SMRs and other pharmacological agents. Male mice (n ≥ 5) were given test drugs p.o. followed by morphine sulfate [15 mg/kg subcutaneously (s.c.)] 15 min later. The mice were scored all or none for a Straub tail reaction 45 min later. Graded doses of active compounds were further evaluated for ED50 estimation by probit analysis. ED50 values (mg/kg) were estimated for the following compounds: baclofen (6.4), chlorpromazine HCl (3.8), cyclobenzaprine HCl (24.6), dantrolene Na (14.4), diazepam (8.3), haloperidol (6.2), naloxone HCl (8.7), phenoxybenzamine HCl (47.6), phentolamine HCl (265), and trifluoperazine HCl (25.4). These ED50 values appeared to correlate with initial adult human daily oral doses for muscle relaxation. The following compounds inhibited the Straub tail response in ≤ 40% of the mice tested at the doses indicated (mg/kg): carisoprodol (300), lidocaine (100), mephenesin (300), phenytoin (100), procainamide HCl (100), procaine HCl (100), propranolol HCl (100), quinidine sulfate (100); and all selected calcium‐channel blockers (30), antidepressants (30), and neuromuscular blocking agents (> 10 times the literature i.p. ED50 values with the exception of gallamine triethiodide at 30 mg/kg) that were tested. Pentobarbital Na was active only at doses that impaired the righting reflex. This animal model was thus determined to be useful for evaluating SMR efficacy and in predicting.

Two automated locomotor activity tests for dopamine autoreceptor agonists

In the first test (exploratory activity), pretreated rats explored a novel environment in the dark. The potential autoreceptor agonists apomorphine HCl, N-n-propylnorapomorphine (NPA), and N-n-propyl-3-(3-hydroxyphenyl)-piperidine (3-PPP) and its enantiomers decreased the total distance travelled while at the same time paradoxiacally increasing the number of discrete movements. This is a very different pattern from that of the typical antipsychotic drugs haloperidol HCl and chlorpromazine HCl, and the atypical antipsychotic drug clozapine, which also decreased the total distance travelled but decreased the number of movements. Both groups decreased the distance/movement. In the second test, rats were habituated to the monitors in the light and then treated with test drug and stimulant (d-amphetamine sulfate or apomorphine HCl). Apomorphine HCl, NPA, and (+)3-PPP antagonized amphetamine-stimulated locomotor behavior (total distance) without antagonizing apomorphine-stimulated behavior, suggesting a presynaptic dopamine autoreceptor agonism. EMD 23448 gave equivocal activity. On the other hand, haloperidol HCl, chlorpromazine HCl, and clozapine decreased both amphetamine- and apomorphine-stimulated behavior, suggesting a postsynaptic dopamine antagonism. 3-PPP and (−)3-PPP showed neither pattern in this test.

Possible involvement of calmodulin in apical constriction of neuroepithelial cells and elevation of neural folds in the chick.

Chlorpromazine and trifluoperazine HCl, antipsychotic drugs known to bind to calmodulin, reversibly inhibited elevation of neural folds by interfering with the contractile activity of apical microfilament bundles in developing chick neuroepithelial cells.

Chlorpromazine and lithium interaction: A biochemical and histological study

Biochemical and histological studies on the effect of separate and combined administration of LiCl and of chlorpromazine (CPZ) on female C 57BL 6J mice were performed. Mice were divided into 4 groups. One group was given an intraperitoneal injection daily of CPZ HCl, 5 mg/kg for 4 days followed by 4 more days of a daily dosage of 10 mg/kg. A second group was maintained on 0.4% ( w v ) LiCl solution as the sole drinking fluid for 8 consecutive days and a third group received the same LiCl solution but with daily CPZ injection as the initial group for 8 days. The fourth group served as saline-controls. Hepatic liver alcohol dehydrogenase was induced by combined drug treatment from respective controls. The Li-treatment inhibited mitochondrial liver aldehyde dehydrogenase, and coadministration of CPZ with LiCl antagonized this effect. Mice treated with CPZ showed corneal cellularity and mitotic figure appearance without inflammation. The LiCl treated mice displayed variations in base corneal cell size, shape and pigmentation with aggregation of the nuclei, and the presence of mitotic activity without inflammation. Mice receiving combined drug treatment showed similar corneal alterations, but mitotic figures were found above base cell layer suggesting an enhanced corneal toxicity. The results suggest a drug-drug interaction phenomenon which may explain some of their adverse reaction when given concurrently.

EFFECTS OF CHLORPROMAZINE, IMIPRAMINE AND BACLOFEN ON THE SPINAL POLYSYNAPTIC REFLEX IN ACUTE, CHRONIC AND 6-HYDROXYDOPAMINE-TREATED SPINAL RATS

Effects of the drugs affecting monoaminergic neurotransmission were examined on the spinal polysynaptic reflex (PSR) in anesthetized spinal rats. Chlorpromazine HCl (0.5-2.0 mg/kg, i.v.) and baclofen (0.63-2.5 mg/kg) depressed and Imipramine HCl (1.25-5.0 mg/kg) increased the amplitude of PSR in acute spinal animals, recorded as evoked electro-myogram in the gastrocnemius muscle by electrical stimulation of the common peroneal nerve. However, chlorpromazine and Imipramine showed effects neither on PSR in chronic spinal rats, nor in acute spinal rats with the intracisternal administration of 6-hydroxydopamine, which caused depletion of the spinal noradrenaline, dopamine and serotonin, and selective depletion of the spinal noradrenaline, respectively. Baclofen depressed the amplitude of PSR in both preparations with almost the same potency as that in acute spinal ones. Imipramine HCl (2.5 mg/kg, i.v.), chlorpromazine HCl (1.0 mg/kg) and baclofen (1.25 mg/kg) depressed the mono- and polysynaptic heights of the ventral root potentials in acute spinal rats. However, their depression of polysynaptic height was not so strong. These observations strongly suggest that, at the receptor sites on spinal interneurons where the descending monoaminergic neurons terminate, spinal monoamines, especially noradrenaline, are involved in PSR modification by chlorpromazine and imipramine, but not in PSR depression by baclofen.