Phenothiazine drugs

Tompsett125 determined phenothiazine drugs in blood serum by extraction, oxidation with hydrogen peroxide to sulphoxide and evaluation spectrofluorimetrically. 

Strata- Carboxylated styrene- Mixed mode with weak cation Phenothiazine drugs (93) ... 

Drugs that may affect maprotiline include thyroid hormones, benzodiazepines, and phenothiazines. Drugs that may be affected by maprotiline include anticholinergics. 

Another form of parkinsonism is drug-induced, that is, iatrogenic parkinsonism, which often is a comphca-tion of antipsychotic therapy, especially following the use of the butyrophenone and phenothiazine drug classes (see Chapter 34). Unlike idiopathic parkinsonism, striatal content of dopamine is not reduced by administration of these drugs. In contrast, they produce a functional decrease in dopamine activity by blocking the action of dopamine on postsynaptic dopamine receptors. 

Examples of multifunctional sulfides which bond to platinum(II) via the sulfide sulfur are phenoxathiin (184) and the phenothiazine drugs (185).1732,1733... 

Cardiotoxicity is a very well known side effect of phenothiazine drug (see Fig. 1) administration. The main cardiotoxic effect is the induction of different types of arrhythmia, which are mostly the result of QT interval prolongation [242], This prolongation can be associated with a potentially lethal ventricular arrhythmia known as torsades de pointes [242,243]. The mechanism of the influence of phenothiazines on QT interval prolongation is complex, but on the molecular level there is increasing evidence that different types of myocardial ion channels are involved [243]. 

TFP (5) was found to be a very effective blocker of human Kv2.1 potassium channels expressed in human glioblastoma cells [253]. As for other types of channels, for Kv2.1 the TFP-induced block was also dose-dependent (IC50 = 1.21 xM). Some of the other, non-phenothiazine drugs were even more effective blockers for the most potent, fluspirilene (an antipsychotic agent), substantial block was observed at 30 nM. 

PC12) cells. Inhibition of L-type Ca2+ currents by phenothiazine drug was also found in invertebrate neurons. Investigations performed by Cruzblanca et al. [266] revealed that TFP (5) caused reversible and dose-dependent reduction of L-type Ca2+ currents in Helix aspersa (brown snail) neurons. The efficacy of inactivation of this current was enhanced by this drug. The possibility that calcium currents were altered by the influence of TFP (5) on the protein kinase C (PKC) activity was excluded in this paper. 

Large conductance chloride channels (Maxi Cl channels) present in membranes of fibroblast cells were another class of chloride channels that were affected by the presence of phenothiazine derivatives. As described by Valverde et al. [280], these channels become activated by CPZ (9) and tri-flupromazine (11). Activation was dose-dependent for both drugs the half-maximal responses (EC50) were 21 and 23 iM for CPZ (9) and triflupro-mazine (11), respectively. The effects of the drugs were observed exclusively for applications in the extracellular bathing solution. The authors of this paper provided no information about the possible physiological role of Maxi Cl channel activation by phenothiazine drugs. 

There are three main therapeutic applications of the phenothiazine drugs (1) they have an antiemetic effect (stop vomiting) (2) they are used with anesthetics, potent analgesics (pain relievers), and sedatives to permit their use in smaller doses and (3) they are used most widely to relieve anxiety and tension in various severe mental and emotional disorders. 

Any toxicological analysis involves two broad steps the first is extraction of the toxic agent from the biological matrix and the second is identification and quantitation of the isolated material. There are very few useful tests which can be applied directly to body fluids. Exceptions are urine screening tests for salicylate, ethclorvynol, and phenothiazine drugs. 

Trifluoperazine (TFP) is an antipsychotic phenothiazine drug which is bound strongly to brain calmodulin and is a potent calmodulin antagonist. TFP is believed to be bound to... 

Location Reagents. Spray file plate developed m System TA, and one of file plates developed in System TE, with acidified iodoplatinate solution. Lightly spray the remaining plate developed in System TE with 9M sulphuric acid phenothiazine drugs and tiieir metabolites give pink, red, or blue spots. Overspray with acidified iodoplatinate solution the presence of the acid deepens the blue colour produced when morphine reacts with iodoplatinate solution, and this increases the sensitivity of detection of this compound. 

The first synthesis of phenothiazine was reported by Bernthsen about 80 years ago. In the evolution of the chemistry of this heterocycle, three periods can be discerned. First, phenothiazine was of interest owing to its quinonoid derivatives—an important chapter in sulfur dye chemistry. Research work in the field of phenothiazine was then stimulated by the discovery of the anthelmintic action of unsubstituted and of some C -substituted phenothiazines. During the last two decades, the exceptional pharmacological properties of some A-substituted phenothiazines, e.g., the antihistaminic activity of promethazine, 10-(2-dimethylamino-l-propyl)phenothiazine, and particularly the psychotherapeutic action of chlorpromazine, 2-chloro-10-(3-dimethylamino-1 -propyl )phenothiazine, focused interest mainly on the synthesis and testing of a great number of compounds of this type. The phenothiazine drugs now play a very important part in chemotherapy. 

The ion R3NH+ combined with X , present in the molecule of many phenothiazine drugs, used as salts, gives rise to a broad band in the 2300-2500 cm i range. 

A systematic survey of the IR spectra of the principal phenothiazine drugs enabled Warren et al. to distinguish four typical bands in the regions 730-755, 785-800, 840-870, and 915—928 cm i and a characteristic fingerprint which may be used in the identification of these drugs. 

In order to clarify the problem of the position at which metabolic ring hydroxylation of phenothiazine drugs occurs, the nuclear magnetic resonance (NMR) spectra of some substituted phenothiazines were investigated. Although the application of NMR spectroscopy... 

The use of NMR and IR spectroscopy has been recommended for the identification of phenothiazine drugs and detection of impurities in samples of such drugs, inasmuch as the substituents, and particularly the side chain, give rise to characteristic groups of signals. 

Because the biological action of phenothiazine drugs may be due, at least partly, to their interaction with cell membranes, the study of adsorptivity and surface activity of phenothiazines has been carried out by several research groups. 

Debye-ScherrerX-ray diffraction photographs of phenothiazine and of some phenothiazine drugs were taken for analytical purposes by the Colleter group " and others. An exact knowledge of the molecular structure of phenothiazines may be useful to the under-... 

Sulfuric acid was often used, either alone or in conjunction with other oxidants such as ferric salts, to convert phenothiazine drugs and their metabolization products into the colored radical species, which may then be identified and estimated by spectrophotometry. Rieder found the absorption maximum of the... 

Oxidizing agents with metallic cations in higher oxidation states are of interest for the titrimetric estimation of phenothiazine drugs at the same time, there are indications of an interaction existing in vivo between phenothiazines and trace elements. Both these reasons have stimulated research work on the oxidation of phenothiazines... 

The appearance of an intense absorption in the long-wavelength region after irradiation was proposed by Ippen as an in vitro preliminary test to predict possible photoallergic side effects of new phenothiazine drugs structure 24 is tentatively put forward by the same author for the photodecomposition product of chlorpromazine responsible for the allergic reactions. ... 

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