The influence of the bile salts aggregates on the kinetics of chlorpromazine cation radical decay.
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Biomedical subjects
Publications and source records attributed to M Trotta.
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5-Hydroxytryptamine accumulates at pH 6.0 when ATP is present on one side of an artificial lipoidal barrier. In the presence of chlorpromazine, the diffusion of ATP through the barrier and a decrease in the accumulation of serotonin can be noted. The diffusion rate constants of ATP and serotonin are related to the concentration of chlorpromazine.
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The tricyclic amines promazine, promethazine, chlorpromazine, triflupromazine, and trifluperazine form solid ion pairs with ATP in a 1:2 molar ratio. There is a good correlation between the measured Ksp and the apparent diffusion constants of the ion pairs with the critical micelle concentration (CMC) of the corresponding phenothiazines. Solid ion pairs are solubilized by phenothiazine micelles; the binding constants of ATP to drug micelles are calculated from solubility data at 25 degrees C and can be related to the CMC of the phenothiazines.
The lipophilicity of propranolol is increased by some bile salts which form ion-pairs. In the presence of taurodeoxycholate, the logarithm of the apparent partition coefficient (log P) of propranolol is increased. Moreover, the apparent diffusion constants in vitro of propranolol as ion-pairs at pH 3.0-6.0 are about 5-6 times higher than those of propranolol alone. The area under the curve values of plasma concentration-time profiles of propranolol, following its oral administration to rabbits together with taurodeoxycholate, are about 1.4 times higher than those after administration of propranolol alone. Moreover, after the administration of propranolol with taurodeoxycholate the plasma concentration rises more rapidly, with a point of inflection between 0.5 and 1.5 h, than after administration of propranolol alone. Taurodeoxycholate does not modify the first-pass effect of propranolol in rabbits following intravenous and intraportal administration. The absorption of an oral dose of propranolol in the presence of taurodeoxycholate increases from 70% to 100%, due to the higher lipophilicity of the ion-pair. The plasma concentration-time curves suggest the hypothesis that greater absorption of the ion-pair occurs mainly in the upper region of the gastrointestinal tract.
Phenothiazines with bovine hemoglobin give solid complexes in phosphate buffer; this is due to the presence of ion-pairs between phenothiazines and phosphates. Using diluted solutions the number of sites available on each protein molecule and the intrinsic binding constants are determinated; the number of sites, in solutions and in solid complexes, is about the same for each drug, but different for the various phenothiazines.
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The effect of carboxylic acids on the permeation of chlorpromazine was investigated through a dimethyl polysiloxane nonpolar membrane. The permeability of the diffusate, at pH 5.8, increases considerably in the presence of carboxylic acids or phosphate, probably due to an ion-pair formation between the relative anions and chlorpromazine.
Complexation between oppositely charged antidepressant drugs and porphyrin derivatives was investigated by NMR spectroscopy. The solid complexes obtained are soluble in antidepressant aggregates and a good fit was found between the values of CMC of the drugs and the values of the binding constants of porphyrins with antidepressant micelles.
A sensitive method based on ion-pair extraction is described for the quantification of hematoporphyrin and protoporphyrin using chlorpromazine as an ion-pair-forming agent. Extraction of the ion-pair in chloroform is obtained quickly at an optimum pH of 6.5 for hematoporphyrin and 6.5-6.8 for protoporphyrin, giving an excellent recovery of the porphyrin. A stoichiometric relationship of 1:2 between porphyrin and chlorpromazine is proved. Cyanocobalamin and liver extract do not interfere with the assay.
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An o/w microemulsion formulated using lecithin and an alkyl glucoside as mild, non-irritant surfactants was proposed as a cosmetic vehicle for arbutin and kojic acid, naturally occurring whitening agents. After assessing the physicochemical stability of the microemulsion in the presence and absence of whitening agents, several perfumed compositions, developed using fragrant molecules of natural or synthetic origin, were introduced, and the olfactory impact of the perfumed microemulsion was evaluated. The photostability to UVB irradiation of both whitening agents was determined in aqueous solutions and in microemulsions, and also in the presence of the perfumed compositions. The stability of arbutin and kojic acid was higher in microemulsions than in aqueous solutions, and only in some cases did the presence of odorous molecules appear to influence it: linalool exerted some protective effect towards kojic acid photodegradation.