Interaction of carbamazepine and chlorpromazine in rabbits.

The interaction of carbamazepine and chlorpromazine in rabbits has been studied. The drugs were administrated as single oral doses (200 mg of each drug). The sequence of administration of the drugs was varied. It has been established that by simultaneous administration these drugs decrease absorption of each other in plasma. This may be explained by competition of the drugs to transfer from the gastrointestinal tract into plasma, as well as by the formation of complexes, more or less stable and more or less bound to gastrointestinal tissues. Carbamazepine intensifies the biotransformation of chlorpromazine, which may be caused by the ability of carbamazepine to induce microsomal liver enzymes. Chlorpromazine suppresses the biotransformation of carbamazepine, however. This may be caused by intensive capture of chlorpromazine by liver tissues and by its intensive biotransformation, which in turn is conditioned by its surface-active nature and by the increase of its metabolism with carbamazepine. Therefore the biotransformation of chlorpromazine is increased and metabolism of carbamazepine is reduced. The sequence of administration of the drugs affects their pharmacokinetics significantly.     

Synthesis of possible metabolites of chlorpromazine. I. 7-hydroxy derivatives of chlorpromazine,nor1-chlorpromazine and nor2-chlorpromazine

The title compounds and various derivatives have been prepared as analytical standards for the identification of chlorpromazine metabolites in biological materials. Additional evidence is presented for the existence of a halogen-induced Smiles rearrangement in the phenothiazine series.     

Dye-sensitized photooxidation of chlorpromazine

Chlorpromazine efficently quenches singlet oxygen (¹O₂) with a k_q = 3.5 × 10⁷ M^?1 s^?1. The major result of the chemical interaction between these two species is the cleavage of the N-side chain.     

Voltammetric determination of chlorpromazine hydrochloride

The electrochemical behaviour of chlorpromazine hydrochloride (CPZ-HCI) in sulphuric acid was investigated voltammetrically using ruthenium electrodes and it was subsequently determined by the same method. From the recorded voltammograms it was concluded that CPZ-HCI can be determined in the concentration range 2 x 10(-4)-8 x 10(-4) M (71-284. 3 micrograms ml-1). The proposed voltammetric method was applied to the determination of CPZ-HCI in tablets used for neuroleptic purposes in Turkey; the amount of effective compound was found to be within the ranges given for a pharmacopoeial procedure.     

13C NMR spectral analysis of chlorpromazine,chlorpromazine sulfoxide and related models

The natural abundance carbon-13 nmr spectra of chlorpromazine, chlorpromazine sulfoxide and related models were obtained and assigned. The chemical shift effects from sulfoxidation of the carbon skeleton will be discussed. Assignments were made on the basis of models, single frequency off-resonance decoupling experiments, additivity rules based on benzene substituent effects, and general symmetry considerations.     

Some hydroxylated derivatives of chlorpromazine

As part of a program to determine the metabolic fate of chlorpromazine [2-chloro-10-(3-dimethylaminopropyl)phenothiazine] (I), the synthesis of several hydroxylated derivatives of I was undertaken. This paper reports the preparation and structural verification of the 1- and 6-hydroxy and the desdimethyl 3-hydroxy derivative, and summarizes unsuccessful attempts to prepare the 4-hydroxy derivative of I.     

Synthesis of a non-flexible analog of chlorpromazine

9-Chloro-2-dimethylaminomethyl-1,2-dihydropyrrolo[3,2,1-kl]phenothiazine (3b), a conformationally restricted analog of chlorpromazine, has been synthesised and has been found to be devoid of neuroleptic activity.     

Properties and analytical application of chlorpromazine picrate

In neutral medium, picric acid (PA) reacts with chlorpromazine (CPM) hydrochloride with the formation of an orange compound, sparingly soluble in water, of molar ratio PA:CPM = 1:1. The compound is thermally stable up to a temperature of about 200 degrees C. The m.p. (178 degrees C) can be used for identification of picric acid as well as of chlorpromazine hydrochloride. Chlorpromazine picrate is extracted quantitatively with benzene, and the extract can be used for colorimetric determination of chlorpromazine hydrochloride. Beer's law is obeyed in the CPM concentration range 10-60 mug/ml.     

Synthesis of possible metabolites of chlorpromazine. II. 3-, 8- and 9-hydroxychlorpromazine

The title compounds have been prepared as analytical standards for the identification of chlorpromazine metabolites in biological materials. Unequivocal structural proof of key compounds was accomplished by using at least two unrelated syntheses for each one. Resistance of some phenothiazines to preparation via classic Smiles rearrangement is discussed. More examples are offered of halogen-induced Smiles rearrangement. A rare example of phenothiazine polymorphism is presented.     

Ab initioLCAO-MO-SCF Calculation of chlorpromazine and promazine

Ab initio LCAO -MO -SCF Gaussian basis function calculations have been performed for chlorpromazine and promazine. By prescreening for the size of the integrals before calculation, it was only necessary to calculate 12 million out of the possible 38.5 million integrals for chlorpromazine. By a novel procedure of processing the integral tapes for the SCF it was possible to cut down significantly on the amount of time for the SCF . The SCF calculations converged smoothly for both promazine and chlorpromazine. There is a sizeable energy gap between the energy of the highest occupied molecular orbitals in these molecules (which is of the order of ?0.3 a.u.) and the lowest unoccupied molecular orbital (which is of the order of + 0.15 a.u.). The gross atomic populations of chlorpromazine and promazine resemble each other and differ only somewhat on the carbon atom to which the substituent is attached and the carbons and their hydrogens adjacent to it.     

13C NMR spectral assignments of chlorpromazine and its 5-oxide. Literature correction

The ¹³C chemical shift assignments of title compounds were made on the basis of their coupled and decoupled spectra. The size of the ipso and allylic ¹³CH coupling constants establish unequivocally the identity of symmetry related carbon pairs and show that several assignments reported previously are incorrect.     

The singlet oxygen oxidation of chlorpromazine and some phenothiazine derivatives. Products and reaction mechanisms

A kinetic and product study of the reactions of chlorpromazine 1, N-methylphenothiazine 2, and N-ethylphenothiazine 3 with singlet oxygen was carried out in MeOH and MeCN. 1 undergoes exclusive side-chain cleavage, whereas the reactions of 2 and 3, in MeOH, afforded only the corresponding sulfoxides. A mechanism for the reaction of 1 is proposed where the first step involves an interaction between singlet oxygen and the side-chain dimethylamino nitrogen. This explains why no side-chain cleavage is observed for 2 and 3.     

邻二氮菲分光光度法测定盐酸氯丙嗪

在HAc-NaAc缓冲介质中,盐酸氯丙嗪(CPZ)能定量使Fe(Ⅲ)还原为Fe(Ⅱ),还原生成的Fe(Ⅱ)与邻二氮菲反应生成稳定的红色络合物,并且在一定范围内,CPZ的浓度和生成的红色络合物的吸光度呈良好的线性关系。据此,提出邻二氮菲-Fe(Ⅲ)体系测定盐酸氯丙嗪的新方法。在优化的实验条件下,盐酸氯丙嗪的质量浓度在0.040～15.00 mg/L范围内与吸光度呈现良好的线性关系,线性相关系数R=0.9995,摩尔吸光系数ε=2.8×104 L.mol-1.cm-1,检出限为0.020 mg/L。11次重复测定的相对标准偏差小于2.9%。该方法用于药物中盐酸氯丙嗪的测定,结果满意。     

Spectrophotometric determination of chlorpromazine hydrochioride by 1,10-phenanthroline

在HAc-NaAc缓冲介质中,盐酸氯丙嗪(CPZ)能定量使Fe(Ⅲ)还原为Fe(Ⅱ),还原生成的Fe(Ⅱ)与邻二氮菲反应生成稳定的红色络合物,并且在一定范围内,CPZ的浓度和生成的红色络合物的吸光度呈良好的线性关系.据此,提出邻二氮菲-Fe(Ⅲ)体系测定盐酸氯丙嗪的新方法.在优化的实验条件下,盐酸氯丙嗪的质量浓度在0.040～15.00mg/L范围内与吸光度呈现良好的线性关系,线性相关系数R=0.9995,摩尔吸光系数ε=2.8×104L·mol-1·cm-1,检出限为0.020mg/L.11次重复测定的相对标准偏差小于2.9％.该方法用于药物中盐酸氯丙嗪的测定,结果满意.     

Spectrophotometric determination of microgram amounts of chlorpromazine with chloranil

A simple spectrophotometric method for the determination of small amount of chlorpromazine has been developed. The reaction of chloranil as π-acceptor reagent with chlorpromazine was studied. The method is rapid, simple, and relatively sensitive and precise (RSD 1.8%). Beer's law was followed within the approximate concentration range of 50–900 μg in a final volume of 25 ml. Negative deviation was abserved beyond these limits. The general analytical and physical parameters were also established.     

Disposable solid state probe for optical screening of chlorpromazine

We are presenting a simple, low-cost and rapid solid-state optical probe for screening chlorpromazine (CPZ) in aquacultures. The method exploits the colourimetric reaction between CPZ and Fe(III) ion that occurs at a solid/liquid interface, the solid layer consisting of ferric iron entrapped in a layer of plasticized PVC. If solutions containing CPZ are dropped onto such a layer, a colour change occurs from light yellow to dark pink or even light blue, depending on the concentration of CPZ. Visual inspection enables the concentration of CPZ to be estimated. The resulting colouration was also monitored by digital image collection for a more accurate quantification. The three coordinates of the hue, saturation and lightness system were obtained by standard image processing along with mathematical data treatment. The parameters affecting colour were assessed and optimized. Studies were conducted by visible spectrophotometry and digital image acquisition, respectively. The response of the optimized probe towards the concentration of CPZ was tested for several mathematical transformations of the colour coordinates, and a linear relation was found for the sum of hue and luminosity. The limit of detection is 50???M (corresponding to about 16???g per mL). The probe enables quick screening for CPZ in real water samples with prior sample treatment.