Chlorpromazine complexes

The drug substance has been determined by direct potentiometric titration using chlorpromazine-sensitive electrodes [78. These consisted of an electroactive material in the membrane being either the chlorpromazine complex with either tetraphenylborate or dinonyinaphthalene sulfonate set in a PVC matrix. 2-nitrophenyl octyl ether was used as the plasticizer. 

The melanin-chlorpromazine complex may also play a role in reducing the toxicity of chlorpromazine in mice. The LD50 in black mice is more than twice that of chlorpromazine in albino mice. ... 

The multidrug resistance (mdr) reversing effect of the new phenothiazine complexes were tested on mouse T cell lymphoma cell lines. Trifluoperazine (TFP) was much more effective at the same concentration than verapamil. The efficacy of some metal coordination complexes [TFP-Cu(ll) and TFP-V(IV)] exceeded the action of TFP alone. Chlorpromazine (CPZ) or CPZ-Pt(ll) complex had the same or less effect than verapamil or promethazine (Pz) used as a control. 

Chloropentammine Ir (HI) complex, incomplete Ir (III) autoreduction, 39 151-152 Chloroplasts, quantum conversion in, 14 1 1 -Chloroprop-2-ene thermal decomposition, 41 80 Chlorpromazine, reactivity with EDA complexes, 20 333, 336 CH O, 32 374-375 CH3OH, oxidation, 38 21-23 Cholestenone, hydrogenation, 25 57, 58 Cholesterol, biosynthesis of, 25 382 Cholinesterases, stracture of active surface, 10 130... 

Chlorpromazine formed an insoluble 1 1 complex with lead picrate, and 5 3 complexes with the picrates of cadmium, copper, and zinc [70]. The sample (0.1 g) was dissolved in 15 mL of 95% ethanol, and the solution adjusted to pH 9 with 0.1 N NaOH. After adding 25 mL of a 0.02 M picrate reagent (30 mL of Pb), the solution was set aside for 2 hours. The precipitate was collected on a sintered glass fuimel, and the unconsumed metal in the filtrate was titrated directly with 0.02M EDTA at pH 10.4 (after adding 0.5 g of potassium sodium tartrate for Pb). Eriochrome black T was used as the indicator. 

Bhatt et al. have described a method based on the complex formation between chlorpromazine and K3Fe(CN)5 [151]. The latter substance yielded a reduction wave at zero applied potential, and addition of chlorpromazine decreased the wave height in an amount directly proportional to the amount added. Optimum conditions for the determination were reported to be pH 7.4-6.2, use of 0.1 M KCl as the supporting electrolyte, and 0.001% methyl red solution as the maximum suppressor. In this system, chlorpromazine can be determined up to concentrations of 1.4 pg/mL. 

Chlorpromazine hydrochloride in injectable solutions can be measured spectrophotometrically upon formation of the charge-transfer complex with iodine [84]. The complex is formed in an aqueous medium in the presence of excess I2, and is extracted into chloroform for a spectrophotometric determination at 292 and 362 nm. This method is unaffected by exposure to direct light. 

Chlorpromazine reacts with 9-bromomethylacridine in acetonitrile to give a quaternary ammonium derivative, which on subsequent photolysis yields fluorescent products [136]. The fluorescence is linear over the analyte range of 0.05 to 1 pg. Lumogallion 5-chloro-3-(2,4-dihydroxy-phenylazo)-2-hydroxybenzenesulfonic acid forms a fluorescent ion-pair complex with chlorpromazine in the presence of Al(III) which is extracted (without interference from primary or secondary amines) up to equimolar concentrations [137,138]. 

The determination of chlorpromazine after formation of a ternary complex with eosin and Pd(II) was reported [142]. The method employs excitation at 462 nm, and detection of the emission at 545 nm. 

Polyelectrolyte complexes have also been studied as tablet matrices for controlled release applications. For example, the interpolymer complexes of chitosan with pectin and acacia were investigated as tablet matrices for release of chlorpromazine HCL [353]. The complex formed in situ by mixing chitosan with either pectin or acacia displayed the most efficient sustained release (compared to either pectin, acacia or a preformed complex). The results were attributed to the swelling and gel-forming capacity of the freshly formed complex in contrast to the preformed version. 

Meshali MM, Gabr KE (1993) Effect of interpolymer complex formation of chitosan with pectin or acacia on the release behavior of chlorpromazine HC1. Int J Pharm 89 177-181... 

The strength of the NMR method is made evident, for example, in the study of the behavior of phenothiazine derivatives and their EDA complexes in solution [89]. First, the solution properties of, for example, the tranquilizer chlorpromazine hydrochloride and base in a variety of solvents were established leading to the unambiguous notion of self-association and micellization, with the HC1 form being the more stable. Second, the conformation of these compounds in self-adducts were discovered to be virtually unchanged as a function of temperature in the range 20 to 60°C. Iodine stabilized both molecular forms. Third, the complexation sites in these molecules were clearly established, as well as the stoichiometry of the complexes. The stability of these CTC can be followed with time. 

Our conductrimetric work [207] with three hydrochloride psychotropes—chlorpromazine, trifluoperazine, and methotrimeprazine—also showed that these formed charge-transfer complexes with acetylcholine, 6-hydroxydopamine, and noradrenaline which were not highly associated. Two different types of interaction occurred, one in which a single product was formed, and a second which involved two almost simultaneous reactions. In the former case the product was stable to ultraviolet light, while in the latter case the more slowly formed product was strongly UV sensitive. The reactions in solution were first order. 

Antacids containing aluminium and magnesium reduce the gastrointestinal absorption of chlorpromazine and other phenothiazines by forming complexes (625). The clinical significance of this is unknown. 

The number of different metabolic routes which are possible results in a complex mixture of metabolites for many phenothiazines. For example, many of the drugs which contain an AA-dimethyl-aminoalkyl side-chain (e.g. chlorpromazine) are extensively metabolised by A-oxidation, together with hydroxylation, sulphoxidation, and A-dealkylation. 

In a search for a mechanism of the inhibitory action exerted by chlorpromazine on some enzymatic processes, the interaction of this substance with oxidized flavines and xanthines was investigated, and the formation of charge-transfer complexes was observed. There are many indications that the phenothiazine-melanine interaction, which is probably involved in the retinotoxicity of some phenothiazine drugs, is also of the donor-acceptor type, as suggested... 

Photolysis of chlorpromazine (1). The photolysis of 1 results mainly in oxidation to the corresponding sulfoxide. Irradiation in the presence of a cyclodextrin (CD), however, results mainly in dechlorination to promazine (2), which is also converted into a sulfoxide, (3), on photolysis. The rate of conversion of 1 to 2 depends on the cyclodextrin used, the rates following the order /3-cyclodextrin >y-cyck)dextrin> a-cyclodextrin. Since these cyclodextrins differ in the size of the cavity, it appears that the conversion of 1 to 2 takes place within the inclusion complex. ... 

Although it is difficult to predict which drugs are likely to be prone to photodegradation, there are certain chemical functions that are expected to introduce photoreactivity, including carbonyl, nitroaromatic and N-oxide functions, aryl halides, alkenes, polyenes and sulfides. The mechanisms of photodegradation are of such complexity as to have been fully elucidated in only a few cases. We will consider two examples - chlorpromazine and ketoprofen. 

The EDA complexes of chlorpromazine with such electron acceptors as 2,3-dicyanoquinone were much more reactive for the C2D2-HZ exchange reaction than those of phenothiazine with the same acceptors. 

As is shown in Table II, the EDA complexes of chlorpromazine with quinones are much more active than those with trinitrobenzene or pyromellitic acid anhydride, which are stronger electron acceptors. It might be suggested that the )>C=0 groups of quinones interact with the two nitrogen atoms in the chlorpromazine molecule to give active EDA complexes. From the biochemical point of view it is of interest that chlorpromazine forms a stable EDA complex with 2-methyl-a-naphthoquinone... 

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