Drug Metab Dispos. 1997 Apr;25(4):468-80.
In vitro free radical metabolism of phenolphthalein by peroxidases.
Sipe HJ Jr, Corbett JT, Mason RP.
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Phenolphthalein, a widely used laxative, is the active ingredient in more than a dozen commercial nonprescription formulations. Fast-flow EPR studies of the reaction of phenolphthalein with horseradish peroxidase (HRP) and hydrogen peroxide permit the direct detection of two free radicals. One has EPR parameters characteristic of phenoxyl radicals. The other has a broad unresolved spectrum, possibly arising from free radical polymeric products of the initial phenoxyl radical. EPR spin-trapping studies of incubations of phenolphthalein with lactoperoxidase, reduced glutathione (GSH), and hydrogen peroxide with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) demonstrate stimulated production of DMPO/.SG compared with an identical incubation lacking phenolphthalein. In the absence of DMPO, measurements with a Clark-type oxygen electrode show that molecular oxygen is consumed by a sequence of reactions initiated by the glutathione thiyl radical. Enhanced production of DMPO superoxide radical adduct is also found in a system of phenolphthalein, NADH, and lactoperoxidase. In this system the phenolphthalein phenoxyl radical abstracts hydrogen from NADH to generate NAD., which is not spin trapped by DMPO, but reacts with molecular oxygen to produce the superoxide radical detected by EPR. In the absence of DMPO, the oxygen consumption is measured using the Clark-type electrode. Production of ascorbate radical anion is also enhanced in a system of phenolphthalein, ascorbic acid, hydrogen peroxide, and lactoperoxidase. Ascorbate inhibits oxygen consumption when phenolphthalein is metabolized in the presence of either glutathione or NADH by reducing radical intermediates to their parent molecules and forming
Pharm Acta Helv. 1997 Apr;72(2):75-80.
Study of the swelling capacity of a mild laxative formulation.
Barcia Hernandez E, Gil Viejo E, Cadorniga Carro R.
Departamento de Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
In this work, the swelling index is determined for various vegetable fibers (wheat bran. orange fibre and lemon fibre), and several granulated formulations to which different binding agents are added. The formulation that presents the highest swelling index (14.5 ml/g) was found to be composed of orange fibre, lemon fibre and pectin in a 1:1:1 proportion (OF + LF + PH). A study of the evolution of the swelling with time is also carried out, finding that the greatest volume increase is produced between 5 and 10 min from the start of the test. The application of the sigma-minus type calculation to the swelling rate curves produces correlation coefficients higher than 0.9. It is found that the swelling rate constant for lemon fibre is much lower than that of orange fibre. The addition of pectin lowers the swelling rate constant while the gum guar and polyvinylpyrrolidone increase the said constant. In addition, a general exponential equation is deduced which can be applied to all of the cases studied.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9112829&dopt=Abstract constipation laxative
Pharmacology. 1988;36 Suppl 1:40-8.
Effect of sennosides and related compounds on intestinal transit in the rat.
Department of Pharmacology, Dr. Madaus GmbH & Co., Cologne, FRG.
The effect of pure sennosides A + B on large intestinal transit (LIT) was investigated in the rat. LIT was defined as the time from intracecal administration of a color marker through a chronically implanted catheter until first appearance of colored feces. Sennosides (50 mg/kg, administered orally 2-24 h before the marker) reduced LIT from greater than 6 h in controls to a minimum of 30-20 min after a 4- or 6-hour pretreatment. Longer pretreatment times increased LIT again reaching normal values after 24 h. Intracecal administration of sennosides and their natural metabolites (sennidins A + B, rhein-9-anthrone, rhein) simultaneously with the marker accelerated LIT to approximately 50-70 min. The laxative effect was less pronounced after rhein compared with the other compounds. Indometacin, loperamide, and calcium-channel antagonists (verapamil, nifedipine) partially antagonized the effect of intracecal sennosides on LIT and delayed, but did not suppress, appearance of soft feces.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3368525&dopt=Abstract constipation laxative
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