Phenothiazine derivatives interaction

The interactions of TDZ (6) with model membranes composed of different phospholipids were also studied by the same group [78]. Calorimetric studies demonstrated that TDZ (6) altered the thermotropic properties of negatively charged DMPC membranes to a larger extent than of zwitterionic phospholipids (PC and PE). The character of the drug-induced changes of the transition parameters of all studied lipids indicated that TDZ (6), similarly to other phenothiazine derivatives, was likely to be localized close to the po-lar/apolar interface of the bilayers. Experiments in which fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was employed revealed that TDZ (6) reduced the mobility of lipid molecules in a concentration-dependent manner and thus decreased membrane fluidity. The influence of TDZ (6) on isolated... 

The newly synthesized phenothiazine derivative 2-trifluoromethyl-10-[4-(methanesulfonylamido)butyl]-phenothiazine (FPhMS, see Fig. 1 for chemical structure) was also extensively studied in the context of its interaction with lipid bilayers. DSC was used to study the influence of this compound on model membranes formed from DMPE [80], DPPC [81], DMPC, and DMPG [82]. In all the studied lipid systems FPhMS (16) lowered Tm, caused broadening of transition peaks, and induced the decrease of AH. Melting temperatures were found to be reduced by the phenothiazine derivative to a similar extent when different lipids possessing acyl chains of the same length were compared. 

Apart from causing very well known cardiotoxic effects, phenothiazine derivatives can accumulate in lung epithelial cell membranes and therefore cause severe respiratory disorders. In the study performed by Ito et al. [279] it was found that CPZ (9) inhibited transepithelial Cl transport, mainly due to two mechanisms influence on the beta-adrenergic receptor and inhibition of basolateral potassium channels. The authors of this study also suggested that the recorded effects could result from the electrostatic interactions between the drug molecules and negatively charged components of the inner leaflet of the plasma membrane. 

Recently, the tranquilizer action of phenothiazine derivatives has been connected with the flexibility of their molecules. They form complexes with charge transition. These complexes have been obtained as a result of the interactions between phenothiazine derivatives, dextrans, and pectins. IR spectroscopy. X-ray diffraction, UV spectroscopy, and Dreiding models (a 3-D research model) have been applied. " Hypochromic effects (changes in the band s intensity) in UV spectra have been observed. The degree of complex binding correlates with the concentrations of dextrans. 

A. A. Hidalgo, W. Gaetano, M. Tabak and O. N. Oliveira. Interaction of two phenothiazine derivatives with phospholipid monolayers. Biophys. Chem., 109, 85-104, (2004)... 

Compilation and Interactions of Phenothiazine Derivatives in Organized Media... 

Because of the potentially useful pharmacological and biological applications of phenothiazine derivatives, it is very important to investigate the physicochemical aspects of their interactions and aggregations within organized media, such as CDs and micelles of surfactants. As a consequence, several literature studies have been reported in this field [35-44],... 

Hendrich et al. [155] investigated the mechanism of incorporation of phe-nothiazines in the membrane bilayer lipids. They studied the influence of a particular phenothiazine derivative, TFZ, on the thermal properties of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylethanolamine by microcalorimetry. The main phase transition of both lipids was affected by this drug, depending on its concentration. The results suggest that TFZ was probably incorporated into both dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylethanolamine bilayers. The phase separation was presumably induced by the different modes of the drug-bilayer interactions of protonated and unprotonated forms of TFZ. Only phosphatidylcholine, which possesses polar heads less densely packed in bilayers than phosphatidylethanolamine ones, was able to distinguish between the different protonated forms of TFZ. 

Phenothiazine cholinesterase inhibitors. Synthetic derivatives of phe-nothiazine are well-tolerated drugs against a variety of human ailments from psychosis to cancer. A number of synthetic N-10-carbonyl phenothiazine derivatives, with cholinesterase inhibitory activity, were tested for interaction with a variety of neurotransmitter receptor systems. Phenothiazines can be prepared without significant neurotransmitter receptor interactions while retaining high potency as cholinesterase ligands for treatment of AD [165],... 

Examples will now be considered of the application of electrochemical techniques to the interactions of chlorpromazine and other phenothiazine derivatives, heparin, and antibiotics. 

Chlorpromazine plus iodine is not a combination that is likely to occur in a pharmaceutical formulation nor is the interaction of any significance in therapeutics. The study of the reaction is of biological importance, however, because of the information provided with respect to the electronic properties of the phenothiazine derivatives, and these properties in turn are likely to have significance in understanding the underlying mechanisms of the drug. That is, CPZ-I2 is a model system. 

Misson, J., Schreurs, A. and Zeegers-Huyskens, T. (1974) Electronic spectrometric study of the interaction of some phenothiazine derivatives and iodine. J. Chim. Phys. Phys.-Chim. Biol., 71, 460-461. 

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