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S Shibanoki

Publications and source records attributed to S Shibanoki.

33 records · Page 2Linked to original sources
PubMed1988

Supranormal levels of serotonin and its metabolite after raphe cell transplantation in serotonin-denervated rat hippocampus.

Transplantation of fetal raphe cells (14 days of gestation) into the adult rat hippocampus, 2 weeks following serotonin (5-HT)-denervation with intracisternal injection of 5,7-dihydroxytryptamine, can restore 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in the hippocampus to far beyond normal values. Transplantation into the unilateral hippocampus produces asymmetrical turning behavior after administration of the 5-HT releasor, p-chloroamphetamine (IP), comparable to the behavior reported for rats with 5-HT denervation of the unilateral hippocampus. The effect is blocked by prior depletion of 5-HT with p-chlorophenylalanine (IP). The asymmetry in 5-HT levels are correlated with the behavioral change. These data indicate that a large amount of 5-HT is released from nerve terminals of transplanted raphe cells, and suggest that the supranormal levels of 5-HT and 5-HIAA after raphe cell transplantation are neurochemical correlates of 5-HT hyper-innervation of the hippocampus which has been reported previously.

5,7-Dihydroxytryptamine↗
PubMed1988

A study of the clinical usefulness of dobutamine administered orally.

Dobutamine 300 mg was administered orally to both healthy volunteers and to patients with circulatory failure. After the 300 mg dose of dobutamine, subjects were found to have a higher concentration of the drug in their plasma than the effective levels of 37.5 (SD 2.9) ng/ml (n = 5) normally seen during intravenous infusion of the clinically effective (5 micrograms/kg/min) dose. This increased concentration waned within 90 minutes. A clinical effect of dobutamine on the circulation was observed in both the healthy volunteers and the patients. An increase in the cardiac index of the patients continued longer than 90 minutes. An unidentified substance was noticed on chromatography measuring plasma dobutamine concentrations, which may have contributed to the increased cardiac index, although its chemical formula could not be determined. The results suggest that the oral administration of dobutamine may be expected to have a long-lasting and significant therapeutic effect on patients with chronic circulatory failure.

Administration, Oral↗
PubMed1987

Determination of dosulepin and its metabolite: application of high-performance liquid chromatography with electrochemical detection.

Dosulepin, 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenzo [b,e]thiepin hydrochloride, is a thio analogue of amitriptyline and is used for the treatment of anxiety and affective disorders. The present study developed a simple and sensitive procedure for the determination of this compound and its metabolite, northiaden, by a combination of high-performance liquid chromatography with electrochemical detection. Hydrodynamic voltammograms demonstrated an optimal applied potential at 1300 mV for both dosulepin and northiaden. A mobile phase consisting of 0.1 M acetate buffer-acetonitrile-perchloric acid-trichloroacetic acid (50:50:2:1.5) provided the best separation of the drugs. The extraction procedure, which used a heptane-isoamyl alcohol (99:1) mixture, was successfully applied with a recovery of over 90%. A preliminary pharmacokinetic study was performed by the proposed method.

Animals↗
PubMed1987

Comparative study of phenothiazine derivatives on monoamine metabolism--direct correlation between the concentrations of drugs and monoamine metabolites in the brain.

The pharmacokinetics (distribution and elimination) and pharmacodynamics (biochemical effects on monoamine systems) of phenothiazines including the novel compound, E-0663 (10-[3-(3-hydroxypyrrolidinyl)-propyl]-2-trifluoromethyl phenothiazine), in the central nervous system were investigated concurrently in mice using high-performance liquid chromatography with electrochemical detection. The elimination rate of E-0663 from the brain was longer than that of the classical compounds, chlorpromazine, perphenazine and triflupromazine. The phenothiazine (0.01-100 mumol/kg i.v.) increased the metabolites of catecholamines. Direct correlation analysis was applied to the intracerebral concentrations of the drugs and monoamine-related substances. Significant correlations were observed between the concentrations of drugs and dopamine metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid). The relative potency of the drugs for the effect on the extraneuronal process was promethazine less than chlorpromazine less than E-0663 less than triflupromazine less than perphenazine by covariance analysis. On the other hand, noradrenaline metabolite (3-methoxy-4-hydroxyphenylethylene glycol) also revealed a significant correlation, and the potency was highest in the case of E-0663. These results suggest that E-0663 possessed different pharmacokinetic profiles and a different spectrum in its action on monoamine metabolism from classical phenothiazines. The method described here is simple for comparing the real potency and is useful as a new approach in the biochemical pharmacology of centrally acting drugs.

Animals↗
PubMed1986

Effects of various tricyclic antidepressants on amine uptake.

A comparative study of the ability to block the amine pump was carried out on tricyclic antidepressants including dothiepin and northiaden in vivo. Dothiepin was found to prevent the 6-OHDA-induced depletion of cardiac noradrenaline but not the PCA-induced depletion of intracerebral serotonin. Northiaden, an active metabolite of dothiepin, also possessed the same ability with a greater potency than the parent drug. Neither compound affected the biosynthesis of catecholamines and indoleamine. However, neither dothiepin nor northiaden affected 5-HT uptake, as was also observed with imipramine and amitriptyline. These results suggest that the clinical efficacy of dothiepin may be due to inhibition of the amine pump, especially of the catecholamine uptake mechanism, which is qualitatively the same as for imipramine and amitriptyline.

Amitriptyline↗
PubMed1986

Simultaneous determination of the pharmacokinetics and pharmacodynamics of chlorpromazine in the brain of mice.

The direct correlation analyses between the distribution of chlorpromazine (pharmacokinetics) and the biochemical effects of the drug on monoamine metabolisms (pharmacodynamics) are reported. Both samples for quantitative determination of CPZ and of monoamine transmitters and metabolites were obtained by organic extraction procedures from the same sample. The determinations were carried out by high performance liquid chromatography with electrochemical detection. CPZ affected the concentrations of metabolites of noradrenaline, dopamine and 5-hydroxytryptamine, but not those of the monoamine transmitters themselves. However, simultaneous assay demonstrated differences in effects of the drug on the transmitter systems. The concentrations of HVA and DOPAC were increased over a wide range of intracerebral concentrations of the drug, but those of MOPEG, in the range of higher concentrations. On the other hand, CPZ did not reveal any correlations between the intracerebral concentrations of the drug and 5-HIAA. These results suggest that CPZ affected primarily the dopaminergic system rather than the serotonergic one in the early stage of its biochemical actions. The proposed procedure is demonstrated to be simple and useful as a new approach in biochemical pharmacology. The same procedure can be applicable for other centrally acting drugs.

Animals↗
PubMed1985

Liquid chromatographic determination of free and conjugated 3-methoxy-4-hydroxyphenylethylene glycol with wide-ranging substances related to monoamine metabolism.

A simple and sensitive procedure was developed for the simultaneous determination of substances metabolically related to monoamine transmitters including 3-methoxy-4-hydroxy-phenylethylene glycol (MOPEG) in dissected brain regions of rats using high-performance liquid chromatography combined with electrochemical detection. The tissue sample was homogenized in HCl solution. The homogenate was divided into two portions, of which one was used for the assay of MOPEG after enzymatic hydrolysis with sulfatase. A butanol extraction process was performed on the remaining portion to obtain the sample of monoamine transmitters, precursor amino acids, and acidic metabolites. The monoamines and precursor amino acids were finally recovered in HCl solution, while the acidic metabolites shifted into the alkaline buffer from the organic layer. The basic and neutral substances were separated with a 0.1 M sodium citrate/citric acid buffer system (pH 4.0) containing 1% tetrahydrofuran, and the acidic ones with 0.075 M sodium citrate/citric acid buffer (pH 3.5) containing 1% tetrahydrofuran, 10% methanol, and 12% acetic acid. The steady-state concentrations of three monoamine transmitters (noradrenaline, dopamine, and 5-hydroxytryptamine) were determined together with their precursors and metabolites. Changes in the concentrations of these substances were examined for various drugs, of which the effects had been previously confirmed. The changes reflected putative drug effects and demonstrated that the procedure was applicable to the regional determination of monoamines and their metabolically related substances.

Animals↗
PubMed1984

Determination of chlorpromazine in the blood and brain of mice by high performance liquid chromatography combined with electrochemical detection.

A simple and sensitive procedure was developed for determining the concentration of chlorpromazine (CPZ) in the blood and brain of mice with promethazine as the internal standard. The procedure involves (1) primary extraction by a mixture of heptane and isoamyl alcohol (99:1) in an alkaline condition and (2) determination by means of high performance liquid chromatography with electrochemical detection. The detection limit of CPZ was 0.5 ng for one chromatographic injection. The drug was detectable in a 100 microliters sample of the blood by 6 hr after an intravenous injection of 0.25 mg/kg. The concentration of CPZ was about 40 times higher in the brain compared with that in the blood. The biological half life was estimated to be 87 and 65 min, in the blood and brain, respectively. The proposed method is also applicable for the determination of other phenothiazine derivatives and effective for pharmacokinetic study of the compounds in clinics and laboratories.

Animals↗
PubMed1983

Direct correlation between level of morphine and its biochemical effect on monoamine systems in mouse brain. Evidence for involvement of dopaminergic neurons in the pharmacological action of acute morphine.

The pharmacokinetics (uptake and elimination) and pharmacodynamics (biochemical effects on monoamine systems) of morphine in the CNS were investigated concurrently. ICR mice, weighing about 25 g, were injected intravenously with several doses (2.5-80 mg/kg) of morphine. The animals were killed by microwave irradiation (5 kW, 0.6 sec) at 10 and 30 min, and 1, 2, 4, 8 and 24 hr after the injection. The intracerebral levels of morphine and metabolically related substances consisting of monoamines [noradrenaline, dopamine (DA), 5-hydroxytryptamine (5-HT), 3, 4-dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylacetic acid [homovanillic acid (HVA)], 5-hydroxyindoleacetic acid (5-HIAA), tyrosine and tryptophan] were determined in identical samples by a combination of organic extraction and high-performance liquid chromatography with electrochemical detection. The intracerebral level of morphine was found to depend on the dose injected, and the biological half-life of the drug was estimated to be about 1 hr. The morphine injection (2.5-80 mg/kg) caused significant increases in monoamine metabolites although only slight changes occurred in the concns of parent transmitters. The intracerebral level of morphine was significantly correlated with the ratios DOPAC/DA and HVA/DA (r = 0.7033, P less than 0.0001; and r = 0.6455, P less than 0.0001, respectively). On the other hand, the correlation between the morphine level and 5-HIAA/5-HT was lower than those for DOPAC/DA and HVA/DA. These results suggest that monoamine systems, especially DA, are closely involved in the biochemical effects of morphine. Furthermore, the proposed procedure is demonstrated to be useful as a new approach in biochemical pharmacology, where the direct correlation between the distribution of a drug (pharmacokinetics) and the biochemical effects of the drug (pharmacodynamics) can be measured.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Effect of microwave irradiation on monoamine metabolism in dissected rat brain.

The effect of 5 kW microwave irradiation on monoamine metabolism was investigated in dissected regions of rat brain. Concentrations of intracerebral monoamines and their metabolites were simultaneously determined by means of high performance liquid chromatography with electrochemical detection. The concentrations of noradrenaline, dopamine and 5-hydroxytryptamine were reduced by a 0.5 s irradiation in comparison with those of decapitated animals. When the duration of irradiation was prolonged by 1.5 s, on the other hand, the levels of monoamines were increased. The changes of metabolite concentrations were generally opposite direction for those of parent transmitters. These findings suggest that the microwave irradiation affects those concentrations and that a 1.5 s irradiation is recommended in order to completely inactivate the corresponding enzyme prior to the simultaneous determination of monoamines' related substances in dissected brain regions.

Animals↗
PubMed1982

Modification of calcium fluxes by dimethyl sulfoxide and 2-butoxyethanol in sarcoplasmic reticulum vesicles: a possible mechanism for skeletal muscle relaxation induced by dimethyl sulfoxide.

In order to investigate the mechanism of skeletal muscle relaxation induced by dimethyl sulfoxide, 2-butoxyethanol and dimethyl sulfoxide were examined for their effects on 1) Ca2+ uptake into and efflux from sarcoplasmic reticulum vesicles prepared from rabbit fast skeletal muscle and crayfish tail muscle by the murexide method, 2) ATPase activities of rabbit reticulum vesicles, 3) the isolated phrenic nerve-diaphragm preparation of the rat and 4) crayfish opener muscle preparation. Ca2+ efflux rate from rabbit reticulum vesicles was markedly decreased with increasing concentrations (5-20% v/v) of dimethyl sulfoxide without affecting the maximum Ca2+ uptake by the reticulum. 2-Butoxyethanol showed quite contrary effects. Dimethyl sulfoxide strongly inhibited the activity of basal ATPase rather than of Ca2+-dependent ATPase. 2-Butoxyethanol did not significantly inhibit the activity of basal ATPase, but markedly increased Ca2+-dependent ATPase activity. Antagonisms between dimethyl sulfoxide and caffeine were demonstrated either in contractions of crayfish opener muscles or in the Ca2+ release from crayfish sarcoplasmic reticulum vesicles. These results indicate a possibility that dimethyl sulfoxide reversibly induces skeletal muscle relaxation mainly in the sarcoplasmic reticulum by means of decreasing the rate and the amount of Ca2+ release from the reticulum.

Adenosine Triphosphatases↗
PubMed1978

[Digestant effects of a new digestive enzyme capsule, Excelase, on jejunectomized and pancreato-jejunectomized Beagle dogs (author's transl)].

The digestant effects of a new digestive capsule, excelase containing sanactase, proctase, meicelase, olipase-2S and pancreatic digestive enzyme TA, were investigated in vivo. Jejunectomy and pancreato-jejunectomy were performed to cause an artificial disturbance of gastro-intestinal digestion and absorption in Beagle dogs. Absorption of protein and fat was measured using chromic oxide as an indicator. Excelase (3 capsules/dog/day) was given orally to Beagle dogs 1 week after each operation for 7 weeks. Changes in body weight and absorption of protein and fat were observed during the administration. The decrease in body weight of dogs treated with excelase fully recovered, however, that of controls remained even 8 weeks after the surgery. Absorption of protein and fat in the groups of dogs treated with excelase was greatly improved as compared with controls. The digestant effects of excelase on percent absorption of protein and fat were more manifest in pancreato-jejunectomized dogs than in jejunectomized dogs. These results indicate that excelase is effective for gastro-intestinal disturbances of digestion and absorption. The digestant effects of excelase on starch, protein and cellulose were also investigated in vitro using a gastro-intestinal model.

Animals↗