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We have evaluated the neuronal uptake of 12 neutral and quaternary azaheterocyclic amines that are possible candidates for idiopathic Parkinson's disease via dopamine transporter of striatal synaptosomes. The double-reciprocal plots for dopamine transporter obtained from Wistar rat and C57BL/6 mouse synaptosomes with N-methyl-4-phenylpyridinium cation (MPP+) as a substrate were identical to each other. Neutral beta-carbolines and tetrahydroisoquinolines were unfavorable substrates for dopamine transporter. The quarternization of these compounds strikingly increased the affinity for dopamine transporter with 2-10 times greater Km and 10 times smaller Vmax values than MPP+. Although catechol tetrahydroisoquinolines were weak substrates, their quarternization reduced their original properties as substrates for dopamine transporter. These results provide both topographic and electrogenic information of azaheterocyclic amines for the dopamine transporter-mediated influx. The intramolecular distance between the N-atom and the centroid of the benzene ring could be an important factor for the recognition of binding site of dopamine transporter, and an adequate net charge similar to dopamine would be further required for translocation into the cells.

We studied the effects of nifedipine (NF) on UV-induced photohemolysis of erythrocytes in vitro. A suspension in physiologic saline of crythrocytes separated from the venous blood sample freshly obtained from a dog was prepared and used. NF is a photolabile agent, and this drug was extremely sensitive to the long wavelength (365 nm) of UV light. The most abundant photodegradation product was a nitroso-derivative which changed into a lactam-derivative in the dog erythrocyte suspension with or without irradiation. NF itself showed protective effects against photohemolysis of erythrocytes caused by 365 nm of UV light as well as hypotonic hemolysis. But NF enhanced the degree of photohemolysis under oxygen condition. The photohemolysis enhanced by NF was reduced by thiobarbituric acid, indicating an oxidative stress by a radical intermediate of NF to photohemolysis. On the other hand, the nitroso-derivative reacted with erythrocyte hemoglobin spectroscopically to change into the lactam-derivative. It is considered that NF is a phototoxic agent to cause photohemolysis by producing a radical intermediate with oxygen and unknown species of hemoglobin degraded with the nitroso-derivative of nifedipine photoproduct.

The water absorption behavior of karaya gum ointment, which improves perianal dermatitis following definitive operation for diseases, such as Hirschsprung was investigated to elucidate the mechanisms of its action. Forty percent karaya gum ointment (10g) swelled and absorbed 7. 5 and 16g of saline solution under the experimental condition of after 6 and 24hr, respectively. The water absorption was not saturable during the experimental periods. The linear square root of time plots suggested that the water absorption properties of karaya gum ointment are controlled by the diffusion model of water into ointment, and the observed absorption rate constant of 40% ointment was 0.426g/10gitnin1/2. Distilled water as a tested fluid was absorbed more rapidly than saline solution.The effect of concentration on the absorption behavior for the karaya gum and CMC-Na ointment showed that CMC-Na ointment is more absorbent in intermediate concentrations. The water absorption pattern of ointments containing other high molecular compounds was also studied. The order of water absorbency was CMC-Na, sodium alginate, karaya gum, tragacanth gum and acacia at concentration of 40%. Karaya gum ointment exhibited water absorbency comparable to those of the marketed skin barriers containing karaya gum. These results suggest that the water absorption effect of karaya gum ointment is associated with one of the mechanisms by which it improves perianal dermatitis.

New photodegradation products of nifedipine ( 1 ) have been isolated. They were found in tablets dispensed in the pulverized form by hospitals. 1 decomposed concurrently into six components after storage of 30 days under exposure to normal room light. The main photoproduct was a nitroso derivative ( 2 ) and others were minor. Preparative thin-layer chromatography has been used to isolate the six photodegradation products. The chemical structures of these isolated compounds were identified or estimated by comparison with authentic samples and/or using UV, IR, 1 H NMR, mass spectroscopy, melting point determination, and elementary analysis. From these analyses, it was found that 1 was converted into a cis -azoxy derivative ( 4 ), a trans -azoxy derivative ( 5 ), a N , N ′-dioxide derivative ( 6 ) and a lactam derivative ( 7 ) in addition to 2 and a nitro derivative ( 3 ). Furthermore, it is proposed that 2 is mainly responsible for the formation of these new products ( 4 – 7 ) by photochemical condensation.

Integrity testing of membrane filters was performed using bubble point pressure measurement in order to establish the validation of sterile filtration of intrahospital sterile preparations. The average bubble point values for six 0.2μm hydrophilic and three hydrophobic membrane filters were between 59.5-73.4 psi and 22.4-23.7 psi, respectively, that were satisfied on sterile filtration. No effect of sterilization by autoclaving on the bubble point values of filter was appreciably observed. The bubble point ratio was evaluated on intrahospital sterile preparations. In some of them, the bubble point ratios were below 1.0 because of the decrease in the surface tension of the pharmaceuticals. This suggested that bubble point measurement as an integrity test for sterile filtration was easily done and constituted one of the useful methods for ensuring the quality of intrahospital sterile preparations.

A simultaneous determination of four inorganic cations in cardioplegic solution was examined by indirect photometric ion chromatography (PIC). Cardioplegic solution was diluted 100-fold with 2.5mM copper sulfate aqueous solution, treated with SEP-PEK C18 and ACCELL PLUS QMA cartridges, and then injected into the chromatograph. Large amounts of sodium, potassium and magnesium and small amount of calcium were separated on a Zorbax SCX-300 column with 2.5mM copper sulfate solution as an eluent, and detected as negative absorption peaks by an ultraviolet (UV) photometric detector at 230 nm. Straight calibration curves for the cations were obtained from 0.05 to 1.5mM by using a peak height ratio method. The reproducibility of the data was good enough. When cardioplegic solution was diluted 4-fold with the eluent, the determination of calcium in sample solutions was sufficiently good, in spite of over-loadings of the other cations on column. The results obtained by the PIC method were more accurate than those of the autoanalyzer meth