Journal of Pharmacobio-Dynamics
Online ISSN : 1881-1353
Print ISSN : 0386-846X
ISSN-L : 0386-846X
1 巻, 4 号
選択された号の論文の10件中1~10を表示しています
  • TOSHIHARU HORIE, YUICHI SUGIYAMA, SHOJI AWAZU, MANABU HANANO
    1978 年 1 巻 4 号 p. 203-212
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    Cationic and anionic drugs which have hemolytic activities changed the fluorescence intensity of 1-anilino-8-naphthalene sulfonate (ANS) bound to the human erythrocyte ghost membrane. And there was a correlation between their hemolytic activities and fluorescence changes. Furthermore, ANS itself had a hemolytic activity. So it was indicated that ANS was a usefull compound to study hemolysis. The binding of ANS to the human erythrocyte ghost membrane and hemolysis by ANS were investigated with various concentration of ANS. The following results were revealed. (1) The human erythrocyte ghost membrane has two kinds of binding site for ANS. (2) The first site was already saturated by ANS before hemolysis occurred and the second site was about 50% saturated when hemolysis began. (3) The second site may play an important role in hemolysis.
  • ERIKO TAKEUCHI, YOSHIHISA KUDO, HIDEOMI FUKUDA
    1978 年 1 巻 4 号 p. 213-221
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    The effect of L-dopa on γ-motor system, especially on static γ-activity induced by pinna pinching, was investigated in the anesthetized rats. γ-Activity was detected indirectly as the change in the rate of muscle spindle afferent discharges. L-Dopa (25-100 mg/kg, i. v.) caused a dose-dependent inhibition in static γ-activity. The effect of L-dopa was reduced significantly by the pretreatment with α-methyl-dopa (400 mg/kg, i. p.). On the other hand, the pretreatment with disulfiram (400mmg/kg, i. p.) augmented the inhibitory effect of L-dopa. Phenoxybenzamine hydrochloride (2.5 mg/kg, i.v.) augmented the inhibitory effect of L-dopa, whereas haloperidol (0.025 mg/kg, i.v.) had no influence on the effect of the drug. Amphetamine sulfate (2.5 mg/kg, i.v.) and amantadine hydrochloride (10 mg/kg, i.v.) facilitated static γ-activity, and effects of these drugs were considerably reduced by the pretreatment with disulfiram and inhibited by phenoxybenzamine hydrochloride (10 mg/kg, i. v.). These results suggest that L-dopa exerts its inhibitory effect after being metabolized to dopamine, and that amphetamine and amantadine exhibit their facilitatory actions on the static γ-activity through the noradrenergic pathways.
  • SHIGEO BABA, SHINICHI MORISHITA, YASUJI KASUYA
    1978 年 1 巻 4 号 p. 222-229
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    The measurement of nanogram range of 1-butyryl-4-cinnamylpiperazine (BCP) in the human urine in the presence of its metabolites was successfully performed with stable isotopes and gas chromatograph-mass spectrometer equipped with a multiple ion detector (GC-MS-MID). From the urinary excretion data, the elimination kinetics of BCP was determined. There did not exist any appreciable isotope effect in the urinary excretion kinetics of BCP following oral administration of an equimolar mixture of BCP-d0 and BCP-d5 to a human subject, indicating pharmacokinetic equivalence of the unlabeled and labeled BCP. The technique we employed in this study should demonstrate the general usefulness in determining pharmacokinetic parameters of a drug.
  • KATSUHIKO OKUMURA, HISAHIRO YOSHIDA, RYOHEI HORI
    1978 年 1 巻 4 号 p. 230-237
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    1. The lung accumulation of various drugs has been monitored in the isolated blood-perfused rat lung with artificial ventilation, and the effects of many physiological conditions on the drug accumulation have been investigated. 2. The measurement of the drug disappearance from the perfusate and drug concentration ratio in the lung to the perfusate indicated that many cationic drugs could be concentrated in the lung. In the series of cationic drugs, partition coefficients of drugs were correlated well with drug accumulation by the lung. From these results, it was suggested that the cationic (mainly amino) group as well as the lipophilic group in a molecule were required for lung accumulation of drugs. 3. The concentration ratio of many cationic drugs in the lung to plasma concentration of unbound drugs decreased with increasing concentration of perfusate, and the small contribution of drug partition into the lipoidal component in the lung was observed in the process of drug accumulation. These results indicated that the accumulation of cationic drugs resulted from its saturable and specific binding.
  • YUICHIRO KAMIKAWA
    1978 年 1 巻 4 号 p. 238-245
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    Responses to several drugs were examined in the anaphylactically-desensitized atria of guinea-pigs in vitro, and compared with those in non-sensitized atria. The positive inotropic and chronotropic actions of histamine and catecholamines, or the negative inotropic and chronotropic actions of acetylcholine did not show the significant difference in these atrial preparations. However, the biphasic responses to 5-hydroxytryptamine (5-HT) and dimethylphenylpiperazinium (DMPP), which have indirect actions mediated by autonomic nerves, were significantly modified by the anaphylactic desensitization ; the stimulant action of 5-HT mediated by the released catecholamines was reduced but the vagally-mediated inhibitory action of 5-HT was augmented whereas that of DMPP was reduced. From these results, it is suggested that anaphylactic challenges of the isolated atria from sensitized guineapigs cause some functional changes in the autonomic nervous system innervated to the tissue.
  • HARUHIKO SHINOZAKI, MICHIKO ISHIDA
    1978 年 1 巻 4 号 p. 246-250
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    The effect of concanavalin A (Con A) on desensitization of the glutamate receptor was investigated in the crayfish opener muscle. The depolarization of the crayfish muscle fibre caused by bath applied L-glutamate was greatly augmented after exposure of the muscle fibre to Con A (10-6 M) for more than 30 minutes, whereas the depolarization produced by bathapplied quisqualate was not increased by Con A. This augmentation of the glutamate-induced depolarization was more remarkable in relatively high concentrations of L-glutamate than in lower concentrations. Although both glutamate and quisqualate potentials caused by brief iontophoretic application were not so much affected by previous application of Con A, the decline of the depolarization produced by steady iontophoretic application of L-glutamate and quisqualate was completely prevented after exposure to Con A (10-6 M). The decrease in amplitude of both glutamate and quisqualate potentials induced by train pulses was completely blocked by Con A. The slight depolarization produced by kainic acid was not augmented by previous application of Con A. Con A has no influence upon the refractory form of the receptor but prevented the conversion of the effective form into the refractory one. GABA receptors were not affected by Con A. These results suggest that Con A does not potentiate the depolarizing action of glutamate agonists on the crayfish muscle fibre but prevents the development of desensitization of the glutamate receptor.
  • YASUYUKI NOMURA, YASUNOBU OKUMA, TOMIO SEGAWA
    1978 年 1 巻 4 号 p. 251-255
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    Influence of piperidine and D, L-pipecolic acid, a hypnogenic amine and its possible precursor, on the uptake of L-[3H] noradrenaline (L-[3H] NA), [3H] dopamine ([3H] DA), [3H] 5-hydroxytryptamine ([3H] 5-HT), [14C] GABA and [14C] glycine into P2, fractions of the rat brain and the spinal cord was investigated. Neither piperidine nor D, L-pipecolic acid affected the uptake of L-[3H] NA, [3H] DA, [3H] 5-HT and [14C] glycine at a dose of 10-4M. On the other hand, D, L-pipecolic acid (10-4 M). significantly (p<0.01) inhibited the [14C] GABA uptake but not piperidine (10-4 M). These results suggest that a central cation of piperidine, e. g. sedation and sleep-prolongation, is not due to influence on the high affinity uptake mechanism of monoamines, GABA and glycine into synaptosomes in the central nervous system, and that pipecolic acid might interact with the GABA-ergic system as a neuromodulator.
  • KIYOSHI TATSUMI, TOSHIO OU, HIDEYUKI YAMADA, HIDETOSHI YOSHIMURA, HIDE ...
    1978 年 1 巻 4 号 p. 256-261
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    The metabolism of a widely used veterinary drug, N-(5-nitro-2-furfurylidene)-3-amino-2-oxazolidone (furazolidone) was investigated in vitro and in vivo. When the nitrofuran was incubated with milk xanthine oxidase oxidase supplemented with hypoxanthine, two reduction products were isolated as metabolites from the reaction mixture.One (mp179-180) was identified to be 3-(4-cyano-2-oxobutylideneamino)-2-oxazolidone by mass, ultraviolet and nuclear magnetic resinance spectrometries, from its formation of 2, 4-dinitrophenylhydrazone and by comparison with an authentic specimen.The metabolite was also isolated from the urine of rabbits given orally with fufurazolidone.However, the struc-tuer of another metablite (mp 198(dec.))remains to be clarified.The mutagenicity test showed that the nitrofuran was strongly muragenic against Salmonella typhimurium TA100, while above cyano derivative was above cyano derivativa was completely inactive.
  • TOSHIKIRO KIMURA, HAJIME ENDO, MICHIYO YOSHIKAWA, SHOZO MURANISHI, HIT ...
    1978 年 1 巻 4 号 p. 262-267
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    The absorption of aminopenicillins from rat small intestine was investigated by using the in situ oerfsion technique. Carrier-mediated teansport systems were demonstrated for amonxicillin and cyclacillin. The absorption of amoxicillin and cyclacillin was saturable and inhibited by the short term pretreatment of the intestine with alow concentration of HgCl2. The two penicillins inhibited intestinal absorption to each other. The simultaneous perfusion of dioeotides. L-phenylalanylglycine and glycycine, inhibited the absorption of cyclacillin but not of amoxicillin. Furthermore, only cyclacillin was shown to concentrate aganst agrabient. These data are consistent with the presence of two carrier systems for the active transport of cyclacillin in the intestinal mucosa : one which can be blocked by amoxicillin, and the other by bipeptides. Amoxicillin may be transported by the facilitated diffusion mechanism, the carrier of which seems to be common to one of the carrier systems for cyclacillin transport. No evidence of carrier-mediated transport of a, picillin could be found.
  • PARK EUN-HEE, HITOSHI KATO, YUTAKA KASUYA
    1978 年 1 巻 4 号 p. 268-270
    発行日: 1978年
    公開日: 2008/02/21
    ジャーナル フリー
    The effect of histamine on the contractions induced by neuromuscular transmission in the isolated rat vas deferens was investigated. Histamine, 10-6-10-4M, showed a dose-dependent and reversible inhibition of the induced contractions. When the frequency of stimulation was altered(2.5-20Hz), the inhibitory effect tended to be marked at the lower frequencied. Contractions caused by norepinephrine, 10-5M, were unaffected by histamine, indicating that the inhibitory effect of histamine was not due to a reduced sensitivity of the effector cells to the transmitter. Cimetidine, 7×10-5M, diminished the response to histamine but chlorpheniramine, 10-6M, did not. The results suggest that the inhibitory effect of histamine is mediated via H2-receptors probably located at the adrenergic nerve terminal.
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