Phencyclidine (PCP) is a major drug of abuse in the U. S. Unfortunately, the use of PCP may result in the development of psychotic behavior. PCP-induced psychosis is characterized by confusion, excitation, aggression, paranoia, hallucinations and delusions of grandeur and may evoke violent or suicidal behavior. Therefore, many patients suffering from PCP-induced psychosis have been diagnosed initially as schizophrenic. From this viewpoint, PCP is an important drug for investigating schizophrenia in animals. The neurochemical effects of PCP are not well defined at present, but it has been suggested that it interacts with: 1) dopaminergic neuronal system by releasing dopamine from synaptic vehicles at low doses, 2) serotonergic neuronal system as a direct agonist of serotonin 2 receptors at moderate to high doses, 3) opioidergic system by releasing met-enkephalin and/or by binding to opioid sigma receptors and 4) GABAergic neuronal system as an antagonist. It appears that the serotonergic, opioidergic and GABAergic neuronal systems may regulate the dopaminergic system in the development of PCP actions. The possibility to develope neuroleptics and nootropic drugs of new type, has been also suggested.

抄録全体を表示

The reaction rate constant k of phospholipase D on L-α-dimyristoyl phosphatidylcholine (DMPC) liposome with cholesterol and L-α-phosphatidylinositol (PI) was measured by 8-anilino-1-naphtalenesulfonate fluorometry at pH 5.6 in Hepes buffer.
The concentration of cholesterol which represents the maximum velocity of reaction of the phospholipase D was markedly affected by the addition of the L-α-PI. The optimum concentration of Ca²⁺ which is essential to the enzyme reaction of the phospholipase D decreased by 1/6 from 60 mM to 10mM after the addition of the L-α-PI. The decrease in the optimum Ca²⁺ concentration may be caused by phosphatidic acid which a decomposed product of the L-α-PI. The concentration of cholesterol showing the maximum rate constant k of phospholipase D decreased by the addition of L-α-PI from 26 mol% to 18 mol% in the presence of 60mm Ca²⁺ at pH 5.6.
The rate constants of phospholipase D were largely dependant on the reaction temperature when a small amount of cholesterol was added, while those were almost independent of the reaction temperature when the concentration of Ca²⁺ was low.

抄録全体を表示

From the fronds of two Hypodematium species (H. fauriei TAGAWA and H. crenatum KUHN), mangiferin (I), irifiophenone 3-C-β-D-glucoside (VI) and kaempferol 3-O-β-D-glucoside (VII) were isolated. From the fronds of Gymnocarpium robertianum NEWM.(G. jessoense KOIDZ.), a new xanthone glycoside (V, named gymnocarposide) was isolated together with I and 1, 3, 6, 7-tetrahydroxyxanthone (III). The structure of V was elucidated as 1, 3, 6, 7-tetrahydroxyxanthone 1-O-β-D-quinovoside. The chemotaxonomical value of these xanthone derlvatives is discussed.

抄録全体を表示

The Fusarium leaf spot disease was caused by Gerlachia oryzae. Infection of this pathogen is initiated by the conidial anastomosis to form a conidial complex on rice plant and then hyphae grown from the conidial complex invaded the plant tissue through stomata and injured parts. The promoting substances for the conidial anastomosis in the first stage of infection may be involved in the rice plant. We tried to search the promoting substances for the conidial anastomosis of G. oryzae and 8 suger lactones (1-8) were isolated from the rice plant extract. Their activities for the conidial anastomosis were tested.

抄録全体を表示

The correlation between the quality and constituents of various kinds of agalwood, obtained in Hong Kong market at the same time was investigated by the dualwavelength thin layer chromatography scanner comparing with the standard samples of 2-(2-phenylethyl) chromone derivatives, AH₁ (agarotetrol) and AH₂ (isoagarotetrol). It was inapplicable to use AH₃, AH₄, AH₅, and AH₆ owing to their low content, but the total content of AH₁ and AH₂ was relative to the grading of agalwood obtained in the market with few exceptions. The remarkable property of the agaiwood named “Kananko” which has been dealt in on the market at the top price was indicated with very high integrated value obtained by the scanning at the wave1ength ofλ_s 270 and λ_R 400 nm, suggesting a great quantity of other constituents di fferent from chromone derivatives.

抄録全体を表示

A reversed-phase high performance liquid chromatographic method for the determination of some peptides including growth-hormone releasing factor was studied.
For the column packing, the endcapping of residual silanol groups of silica gel was important to obtain symmetric elution peak with high resolution, especially for basic peptides. Other parameters were optimized as follows: particle size, 5μm pore size, 100A; stationary phase, C₁₈.
For the mobile phase, a mixture of acetonitrile and 0.1% trifluoroacetic acid containing 0.1M sodium chloride was selected. Species and concentration of the salt and the counter ion, and pH of the mobile phase had a great influence on selectivities among peptides. The addition of the salt improved column efficiency and peak symmetry, and was effective to establish the analytical conditions in isocratic elution.
Under these chromatographic conditions, coefficient of variations in repetitive injections of each peptide were below 0.65%.

抄録全体を表示

The stereochemical compositions of D-32, propranolol and their glucuronides in the plasma of dog and rat were determined after a single administration 10-30 mg/kg oral dose of stable isotope labeled pseudoracemates of D-32 and propranolol. The parent drug and glucuronic acid conjugates after enzymatic hydrolysis were analyzed by gas chromatography-mass spectrometry (GC-MS) after trifluoroacetate derivatization. The amounts of these diasteroisomers varied inanimal species, in dog Plasma level (-)-isomer was 2-4 fold higher than its isomer whereas in rat the (-)-isomer was equal to the (+)-enantiomer.
Similar species-related differences were observed in the in vitro formation of the isomeric D-32 glucuronidations. The diastereomeric glucuronidations of (-)-and (+)-enantiomers formed by incubating the racemic drug with animal liver microsomes were also quantitated by GC-MS. The values for the apparent K_m on the glucuronidation in dog liver microsomes were 0.87 and 0.63nm, and those of the Vmax. were 11.1 and 1.7nmol/ min/100mg for (-)-and (+)-D-32, respectively. The glucuronidation in the dog and rabbit liver occurred stereoselectively with 3 to 4 fold more (-)-D-32 glucuronide than its isomer, whereas in rat the glucuronidation was less stereoselective. The higher oral bioavailability of (+)-D-32 and (+)-propranolol in dog is suggested to be due to stereoselective presystemic hepatic removal of (-)-propranolol by glucuronidation.

抄録全体を表示

The possibilities of degradation of nitrazepam and its methyl derivative (nimetazepam) in the presence of human faecal flora were investigated. After combination of nitrazepam or nimetazepam with sterilized broth (pH 7.10, 7.18), 1%(pH 6.63, 6.72) or 8%(pH 6.20, 6.37) sterilized stool culture without further anaerobic precautions, the drugs did not degrade in an incubation mixture. This indicates that the drugs did not react with the components of broth and stool cultures, and were stable at these pH values. On the other hand, after combination of the drugs with 1% or 8% human faecal contents in a broth, the drugs disappeared rapidly in the incubation mixture in proportion to stool concentrations. The metabolite of nitrazepam was identified to be 7-aminonitrazepam by a high performance liquid chromatography (HPLC) and thin-layer chromatography. The degradation patterns of nitrazepam and nimetazepam were followed by HPLC.

抄録全体を表示

Effects of the amount of sorbed water on the solid-state crystallization of amorphous α-, β-, and γ-cyclodextrin (CD) were investigated. Water vapor adsorption isotherms were measured at 40°C for each amorphous CD which was prepared by the grinding in tungsten carbide vibrational mill. At higher relative humidities, the amorphous CDs converted to the carresponding crystal CD hydrates. X-Ray powder diffraction measurements were made after the samples reaehed the water vapor adsorption equilibrium. The crystallization occurred when the amorphous CD took the same water content as that of the hydrate. It was found that α-CD recrystallized in two crystal forms of form I and form II at 61.5 and 79.0% relative humidities, respectively.

抄録全体を表示

The water extracts of Rhizoma Zedoariae, Periostracum Cicadae, Galla Wisteriae, and Radix Hostae showed high antitumor activity against Ehrlich ascites carcinoma cells in vivo. The antitumor constituents in these crude drugs were purified and found as high molecular compounds in all these cases.

抄録全体を表示

The interactions of OKY-1580 and OKY-046 with human serum albumin (HSA) were investigated at pH7.4 and 25°C, regarding the binding affinity and the identification of the binding sites. The binding parameters were determined from the Scatchard plots by use of the equilibrium dialysis data. The binding of OKY-1580 to HSA was about 35-fold stronger than that of OKY-046. The reactions of trinitrobenzenesulfonate and 5-nitroaspirin with HSA, which occur near lysine-199 and tryprophan-214 residues (U site) of the HSA amino acid sequence, were slightly inhibited by OKY-1580. The fluorescence intensity of the tryptophan-214 residue was decreased by the binding of OKY-1580 to HSA, indicating the binding site to be the U site of HSA.

抄録全体を表示