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PubMed1984

The mechanism of action of Na glutamate, lysine HCl, and piperazine-N,N'-bis(2-ethanesulfonic acid) in the stabilization of tubulin and microtubule formation.

Preferential interaction measurements between proteins and monosodium glutamate were carried out to arrive at an understanding of the mechanism of its strong effect on tubulin stability and self-assembly into microtubules. For all proteins studied, i.e. bovine serum albumin, lysozyme, beta-lactoglobulin, and calf brain tubulin, the protein showed a large preferential hydration in the presence of monosodium glutamate. The enhancement of tubulin self-association by monosodium glutamate can be interpreted in terms of the large unfavorable free energy of interaction between the additive and the protein. Preferential interactions were also examined for lysine hydrochloride, which also gave a preferential hydration of the proteins, except for tubulin. The dependence of the preferential hydration parameter on proteins was different for the two additives, suggesting the importance of net electrostatic charges of proteins in their interaction with glutamate anions and lysinium cations. The zero preferential interaction of lysine hydrochloride with tubulin indicates an affinity of the lysine cation for the protein. Both additives increased the transition temperature of proteins. This can be understood in terms of the unfavorable free energy of interaction between the additive and the protein surface, which should be even more unfavorable when the denaturation causes an increase in the surface area.

Alkanesulfonates↗
PubMed1978

The analysis and source of 1-diphenylmethyl-4-nitrosopiperazine in 1-diphenylmethyl-4-[(6-methyl-2-pyridyl) methyleneamino]piperazine: a case history.

Analytical methods were developed to determine whether there was less than one ppm of II in IV. Purified IV contained a compound with the same GC retention time as authentic II on OV-17 and Silar 10C columns, using a FID or a nitrogen/phosphorus detector. The GC-coupled mass spectra contained major peaks at m/e 251 and 167 and the GC-coupled methane CI spectra gave the quasi-molecular ion, m/e 282. However, the CI selected ion monitor indicated three compounds at m/e 282. The nitrosamine II was separated from IV by HPLC on muBondapak C18. The GC-coupled mass spectra of the HPLC nitrosamine fraction had peaks at m/e 251 and 167 and other peaks for a compound of greater MW than II, although the GC retention times were the same. Evidence for II and a decrease in the detection limit to one ppm was obtained with a TEA interfaced with a HPLC. To determine if II was formed from IV, it was exposed to ozone at -78 degrees C in methylene chloride. The DSC, IR and NMR of the product were coincident with those of the standard of II. In other experiments, IV in methylene chloride was exposed to light and dry air in the presence and absence of methylene blue. The PMR and 13C NMR of the product formed in the presence of methylene blue were the same as that of II. It is postulated that this nitrosamine was formed by a singlet oxygen mechanism.

Benzhydryl Compounds↗
PubMed1982

[Effects of (E)-1-[bis (4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl) piperazine dihydrochloride(flunarizine) on cerebral circulation].

Effects of flunarizine (0.3-3 mg/kg, i.v.) on cerebral circulation were compared with those of cinnarizine (0.3-3 mg/kg, i.v.) and papaverine (0.1-1 mg/kg, i.v.) in anaesthetized dogs and cats. In dogs any of the three drugs caused a dose-related increase in vertebral, common carotid, and femoral arterial blood flow, while a transient decrease in renal blood flow was seen. In particular, the vasodilatation caused by flunarizine and cinnarizine was much more marked in the vertebral vascular beds as compared to the other ones. Flunarizine (10 and 30 mg/kg, intraduodenally) caused a greater and more prolonged increase in the vertebral blood flow than cinnarizine and papaverine did when they were used in the same doses. Concerning the local circulation in cats, flunarizine and cinnarizine produced a marked flow increase in the cerebellar cortex, and apparent blood flow and pO2 increases in the cerebral cortex with no observable concomitant changes in arterial blood pO2 and pCO2; but a slight decrease in hippocampal blood flow without any consistent effect in hypothalamic blood flow. In this study, flunarizine was shown to have a more prolonged pharmacological activity on the responses of the cerebral circulation than equal doses of cinnarizine or papaverine.

Animals↗